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IMPAIRED FASTING GLUCOSE AND IMPAIRED GLUCOSE TOLERANCE IN OVERWEIGHT AND OBESE INDIVIDUALS AND THE ROLE OF EXERCISE AND WEIGHT REDUCTION TO IMPROVE GLYCEMIC CONTROL
Submitted by
Dr.NAGESWARA RAO ADAPALA MBBS, DNB
Admission number 9277/DFID/2011
A PROJECT REPORT SUBMITTED FOR THE DISTANCE
FELLOWSHIP IN DIABETOLOGY
CHRISTIAN MEDICAL COLLEGE
VELLORE-632004 TAMIL NADU, INDIA
DECLARATION
I hereby declare that this project report entitled “Impaired fasting glucose and impaired glucose tolerance in overweight and obese individuals and the role of exercise and weight reduction to improve glycemic control” has been prepared by me in partial fulfillment of the regulations governing the award of Distance Fellowship in Diabetology (DFID) .
Place : hyderAbad
Date :
Dr .Nageswara rao adapala Mbbs,DNB
Adm no: 9277/DFID/2011
ACKNOWLEDGEMENT
I am extremely fortunate to have Dr. Lakshmi and Dr.Sai Ram as my collegues . I express a deep
sense of gratitude for their advice and help throughout the period of study.
I am grateful to Microsoft office 2007 which made my work easier .
Above all I thank the patients who have co-operated with me in all respects while being
subjected to the study.
INDEX
1.INTRODUCTION – BACK GROUND -01
2.AIMS & OBJECTIVES -27
3.MATERIALS & METHODS -28
4.TERMS USED IN MASTER SHEET AND RESULTS -29
5.RESULTS -30
6.DISCUSSION -37
7.CONCLUSIONS -39
8.BIBLIOGRAPHY -40
9.MASTER SHEET
INTRODUCTION
Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the
phenotype of hyperglycemia. Several distinct types of DM are caused by a complex interaction
of genetics and environmental factors. Depending on the etiology of the DM, factors
contributing to hyperglycemia include reduced insulin secretion, decreased glucose utilization,
and increased glucose production. The metabolic dysregulation associated with DM causes
secondary pathophysiologic changes in multiple organ systems that impose a tremendous burden
on the individual with diabetes and on the health care system.
DM predisposes to end-stage renal disease (ESRD), nontraumatic lower extremity amputations,
adult blindness,cardiovascular diseases. With an increasing incidence worldwide, DM will be a
leading cause of morbidity and mortality for the foreseeable future.
CLASSIFICATION
DM is classified on the basis of the pathogenic process that leads to hyperglycemia, as opposed
to earlier criteria such as age of onset or type of therapy. The two broad categories of DM are
designated type 1 and type 2. Type 2 DM is preceded by a period of abnormal glucose
homeostasis classified as impaired fasting glucose (IFG) or impaired glucose tolerance (IGT).
Table -1 Etiologic Classification of Diabetes Mellitus
I. Type 1 diabetes (beta cell destruction, usually leading to absolute insulin deficiency)
A. Immune-mediated
B. Idiopathic
II. Type 2 diabetes (may range from predominantly insulin resistance with relative insulin
deficiency to a predominantly insulin secretory defect with insulin resistance)
III. Other specific types of diabetes
A. Genetic defects of beta cell function characterized by mutations in:
1. Hepatocyte nuclear transcription factor (HNF) 4 (MODY 1)
2. Glucokinase (MODY 2)
3. HNF-1 (MODY 3)
4. Insulin promoter factor-1 (IPF-1; MODY 4)
5. HNF-1 (MODY 5)
6. NeuroD1 (MODY 6)
7. Mitochondrial DNA
8. Subunits of ATP-sensitive potassium channel
9. Proinsulin or insulin
B. Genetic defects in insulin action
1. Type A insulin resistance
2. Leprechaunism
3. Rabson-Mendenhall syndrome
4. Lipodystrophy syndromes
C. Diseases of the exocrine pancreas—pancreatitis, pancreatectomy, neoplasia, cystic fibrosis,
hemochromatosis, fibrocalculous pancreatopathy, mutations in carboxyl ester lipase
D. Endocrinopathies—acromegaly, Cushing's syndrome, glucagonoma, pheochromocytoma,
hyperthyroidism, somatostatinoma, aldosteronoma
E. Drug- or chemical-induced—glucocorticoids, vacor (a rodenticide), pentamidine, nicotinic
acid, diazoxide, -adrenergic agonists, thiazides, hydantoins, asparaginase, -interferon, protease
inhibitors, antipsychotics (atypicals and others), epinephrine
F. Infections—congenital rubella, cytomegalovirus, coxsackievirus
G. Uncommon forms of immune-mediated diabetes— "stiff-person" syndrome, anti-insulin
receptor antibodies
H. Other genetic syndromes sometimes associated with diabetes— Wolfram's syndrome, Down's
syndrome, Klinefelter's syndrome, Turner's syndrome, Friedreich's ataxia, Huntington's chorea,
Laurence-Moon-Biedl syndrome, myotonic dystrophy, porphyria, Prader-Willi syndrome
IV. Gestational diabetes mellitus (GDM)
Abbreviation: MODY, maturity-onset diabetes of the young.
Source: Adapted from American Diabetes Association, 2011
EPIDEMIOLOGY
The worldwide prevalence of DM has risen dramatically over the past two decades, from an
estimated 30 million cases in 1985 to 285 million in 2010. Based on current trends, the
International Diabetes Federation projects that 438 million individuals will have diabetes by the
year 2030. Although the prevalence of both type 1 and type 2 DM is increasing worldwide, the
prevalence of type 2 DM is rising much more rapidly, presumably because of increasing obesity,
reduced activity levels as countries become more industrialized, and the aging of the population
In 2010, the prevalence of diabetes ranged from 11.6 to 30.9% in the 10 countries with the
highest prevalence (Naurua, United Arab Emigrates, Saudi Arabia, Mauritius, Bahrain, Reunion,
Kuwait, Oman, Tonga, Malaysia—in descending prevalence; There is considerable geographic
variation in the incidence of both type 1 and type 2 DM. Scandinavia has the highest incidence of
type 1 DM (e.g., in Finland, the incidence is 57.4/100,000 per year). The Pacific Rim has a much
lower rate of type 1 DM (in Japan and China, the incidence is 0.6–2.4/100,000 per year);
Northern Europe and the United States have an intermediate rate (8–20/100,000 per year).
Top Ten Countries for Estimated Number of Adults with Diabetes in
Millions
Country 1995 Country 20251 India 19.4 India 57.22 China 16.0 China 37.63 U.S 13.9 U.S 21.94 Russian Federation 8.9 Pakistan 14.55 Japan 6.3 Indonesia 12.46 Brazil 4.9 Russian Federation 12.27 Indonesia 4.5 Mexico 11.78. Pakistan 4.3 Brazil 11.69 Mexico 3.8 Egypt
10 Ukraine 3.6 Japan 8.5All other Countries 49.7 103.6
Total 135.3 300.0
Much of the increased risk of type 1 DM is believed to reflect the frequency of highrisk human
leukocyte antigen (HLA) alleles among ethnic groups in different geographic locations. The
prevalence of type 2 DM and its harbinger, IGT, is highest in certain Pacific islands and the
Middle East and intermediate in countries such as India and the United States. This variability is
likely due to genetic, behavioral, and environmental factors. DM prevalence also varies among
different ethnic populations within a given country.
The global burden due to diabetes is mostly contributed by type 2 diabetes which constitutes 80-
95% total diabetic population.nearly 70% of the people with diabetes live in developing
countries.
The largest number of diabetes are in the 40-59 age groups (132 million in 2010 ) which is
expected to rise further .By 2030 there will be more diabetic people in the 60-70 age groups (196
million)
Type 2 DM in children is becoming common in many countries ,especially so among asian
populations.
PREVALENCE OF DIABETES IN INDIA
The prevalence of diabes in India in 1970’s was 2.3% in urban and 1.55 in rural areas, as shown
by multicentric study by the Indian Council Of Medical Research (ICMR). In 2000s the
prevalence has risen to 12-19% in urban areas and to 4% to 9% in rural areas. A study from rural
Andhra Pradesh reported a prevalence of 13.2%
India which has a large pool of pre –diabetic subjects ( IGT and IFG) shows a rapid conversion
of these high risk subjects to diabtes.the Indian diabetes prevention programme -1 (IDPP-1) has
shown an annual incidence of approximately 18% among subjects with IGT.
Studies of the Prevalence of Niddm in India.*
Year Author (s) Ref PlacePrevalence (%)DM -IGT / IFG
1971 Tripathy et al Cuttack 1.2 ( U)1972 Ahuja et al 17 New Delhi 2.3 (U )1979 Johnson et al Madurai 0.5 ( U)1979 Gupta et al Multicentre 3.0 (U)1984 Murthy et al Tenall 4.7 ( U)1986 Patel Bhadran 3.8 ( R)1988 Ramachandran et al Kudremukh 5.0 ( U)1989 Kodali et al Gangavathi 2.2 ( R)1989 Rao et al Eluru 1.6 ( Rl)1989 Ramachandran et al 3 Madras 8.3 ( U) 8.3 (U)1992 Ramachandran et al 9 Madras 8.2 (U) 8.7 (U)
2.4 (R) 7.8 (R )1995 Ramachandran et al 3 Madras 11.6 (U) 9.1(U)2001 Ramachandran et al 20 NUDS 13.9 (U) 14.4 (U)
2001Indian Task Force on Diabetes
13 PODIS 9.6 (U) 9.71(U)
4.26(R ) 7.49(R )*Ramaiya et al, 1990 - Unless specified otherwise.U URBAN,R RURAL
National studies on diabetes complications are sparse in India. A few population based studies
indicate the prevalence of retinopathy to be 18% to 27%, and overt nephropathy to be about
2.2% with a large percentage (27%) having microalbuminuria.
Peripheral vascular disease is prevalent in 6.3% , peripheral neuropathy in 26% , and coronary
artery disease (CAD) is detected in 21%.
The major contributory factors for the high prevalence of the complications are, delayed
diagnosis of diabetes , inadequate control of glycemia, hypertension and lack of awareness about
the disease among majority of public.
ECONOMIC BURDEN DUE TO DIABETES
The cost of diabetes care is high and escalating world wide.it is estimated by WHO that global
expenditure for diabetes care would increase form 234 billions in 2007 to 411 billions in the next
20 years .over the next 10 years ,lost national income in billions of USD will amount to 555.7 in
China, 303.2 in Russian federation , 336.6 in India , 49.2 in Brazil, and 2.5 in Tanzania
In Asia, the prevalence of diabetes is increasing rapidly and the diabetes phenotype appears to be
different from that in the United States and Europe —onset at a lower BMI and younger age,
greater visceral adiposity, and reduced insulin secretory capacity. Diabetes is a major cause of
mortality
Annual economic burden of Diabetes direct and indirect. Apportioned at individual, Family and Societal Level. *
TABLE 14.Level of Burden
Direct Costs (INR)Indirect Costs (INR)
Total Costs (INR)
RoutineMoni & Lab
Hospital Total
Personal 1882.40 291.10 2551.10 4724.80 1850.50 4024.20Family 4076.80 531.30 6127.50 10735.60 1722.00 5330.10Society 1112.80 124.90 67.50 1305.20 15376.30 16614.00Total 7072.00 947.40 8746.10 16,765.50 18948.80 35714.30* Rayappa PH et al Int.J.Diab.Dev Countries July - Sept 1999.
Table 2 Criteria for the Diagnosis of Diabetes Mellitus
Symptoms of diabetes plus random blood glucose concentration 11.1 mmol/L (200 mg/dL)or
Fasting plasma glucose 7.0 mmol/L (126 mg/dL)or
A1C > 6.5%or
Two-hour plasma glucose 11.1 mmol/L (200 mg/dL) during an oral glucose tolerance test
Abnormal glucose homeostasis is defined as
1.FPG = 5.6–6.9 mmol/L (100–125 mg/dL), which is defined as IFG (note that the World Health
Organization uses an FPG of 6.1–6.9 mmol/L (110 125 mg/dL);
2.Plasma glucose levels between 7.8 and 11 mmol/L (140 and 199 mg/dL) following an oral
glucose challenge, which is termed impaired glucose tolerance (IGT);
3.A1C of 5.7–6.4%.
A1C of 5.7–6.4%. IFG, and IGT do not identify the same individuals, but individuals in all three
groups are at greater risk of progressing to type 2 diabetes and have an increased risk of
cardiovascular disease. Some use the term "prediabetes," "increased risk of diabetes" (ADA), or
"intermediate hyperglycemia" (WHO) for this category.
The current criteria for the diagnosis of DM emphasize that the A1C or the FPG as the most
reliable and convenient tests for identifying DM in asymptomatic individuals.
The global burden due to diabetes is mostly contributed by type 2 diabetes which constitutes 80-
95% total diabetic population.nearly 70% of the people with diabetes live in developing
countries.
The largest number of diabetes are in the 40-59 age groups (132 million in 2010 ) which is
expected to rise further .By 2030 there will be more diabetic people in the 60-70 age groups (196
million)
Risk Factors for Type 2 Diabetes Mellitus
1 Family history of diabetes (i.e., parent or sibling with type 2 diabetes)
2.Obesity (BMI 25 kg/m2),apple shaped figure
3.Physical inactivity,
4.Race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific
Islander)
5.Previously identified with IFG, IGT, or an A1C of 5.7–6.4%
6.History of GDM or delivery of baby >4 kg (9 lb),
7.Hypertension (blood pressure 140/90 mmHg)
8.HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL (2.82
mmol/L)
9.Polycystic ovary syndrome or acanthosis nigricans
10.History of cardiovascular disease
11.age > 45 years
12.low birth weight – greater propensity for DM later in life
Abbreviations: BMI, body mass index; GDM, gestational diabetes mellitus; HDL, high-density
lipoprotein; IFG, impaired fasting glucose; IGT, impaired glucose tolerance. Source: Adapted
from American Diabetes Association, 2011.
Screening
Widespread use of the FPG or the A1C as a screening test for type 2 DM is recommended
because (1) a large number of individuals who meet the current criteria for DM are
asymptomatic and unaware that they have the disorder, (2) epidemiologic studies suggest that
type 2 DM may be present for up to a decade before diagnosis, (3) some individuals with type 2
DM have one or more diabetes-specific complications at the time of their diagnosis, and (4)
treatment of type 2 DM may favorably alter the natural history of DM.
INSULIN BIOSYNTHESIS, SECRETION, AND ACTION
Insulin is produced in the beta cells of the pancreatic islets. It is initially synthesized as a single-
chain 86-amino-acid precursor polypeptide, preproinsulin. Subsequent proteolytic processing
removes the amino-terminal signal peptide, giving rise to proinsulin. Proinsulin is structurally
related to insulin-like growth factors I and II, which bind weakly to the insulin receptor.
Cleavage of an internal 31-residue fragment from proinsulin generates the C peptide and the A
(21 amino acids) and B (30 amino acids) chains of insulin, which are connected by disulfide
bonds.
Secretion
Glucose is the key regulator of insulin secretion by the pancreatic beta cell, although amino
acids, ketones, various nutrients, gastrointestinal peptides, and neurotransmitters also influence
insulin secretion.
Glucose levels >3.9 mmol/L (70 mg/dL) stimulate insulin synthesis, primarily by enhancing
protein translation and processing.
Glucose stimulation of insulin secretion begins with its transport into the beta cell by a
facilitative glucose transporter.Glucose phosphorylation by glucokinase is the rate-limiting step
that controls glucose-regulated insulin secretion. Further metabolism of glucose-6- phosphate via
glycolysis generates ATP, which inhibits the activity of an ATP-sensitive K+ channel.
This channel consists of two separate proteins: one is the binding site for certain oral
hypoglycemics (e.g., sulfonyl-ureas, meglitinides); the other is an inwardly rectifying K+
channel protein (Kir6.2). Inhibition of this K+ channel induces beta cell membrane
depolarization, which opens voltage-dependent calcium channels (leading to an influx of
calcium), and stimulates insulin secretion.
Insulin secretory profiles reveal a pulsatile pattern of hormone release, with small secretory
bursts occurring about every 10 min, superimposed upon greater amplitude oscillations of about
80–150 min.
Incretins are released from neuroendocrine cells of the gastrointestinal tract following food
ingestion and amplify glucose-stimulated insulin secretion and suppress glucagon secretion.
Glucagon-like peptide 1 (GLP-1), the most potent incretin, is released from L cells in the small
intestine and stimulates insulin secretion only when the blood glucose is above the fasting level.
Incretin analogues, are used to enhance endogenous insulin secretion .
Action Once insulin is secreted into the portal venous system, 50% is removed and degraded by
the liver. Unextracted insulin enters the systemic circulation where it binds to receptors in target
sites.
Insulin binding to its receptor stimulates intrinsic tyrosine kinase activity, leading to receptor
autophosphorylation and the recruitment of intracellular signaling molecules, such as insulin
receptor substrates (IRS). IRS and other adaptor proteins initiate a complex cascade of
phosphorylation and dephosphorylation reactions, resulting in the widespread metabolic and
mitogenic effects of insulin.
As an example, activation of the phosphatidylinositol-3′-kinase (PI-3-kinase) pathway stimulates
translocation of a facilitative glucose transporter (e.g., GLUT4) to the cell surface, an event that
is crucial for glucose uptake by skeletal muscle and fat.
Activation of other insulin receptor signaling pathways induces glycogen synthesis, protein
synthesis, lipogenesis, and regulation of various genes in insulin-responsive cells.
Glucose homeostasis reflects a balance between hepatic glucose production and peripheral
glucose uptake and utilization.
Insulin is the most important regulator of this metabolic equilibrium, but neural input, metabolic
signals, and other hormones (e.g., glucagon) result in integrated control of glucose supply and
utilization.
In the fasting state, low insulin levels increase glucose production by promoting hepatic
gluconeogenesis and glycogenolysis and reduce glucose uptake in insulin-sensitive tissues
(skeletal muscle and fat), thereby promoting mobilization of stored precursors such as amino
acids and free fatty acids (lipolysis). Glucagon, secreted by pancreatic alpha cells when blood
glucose or insulin levels are low, stimulates glycogenolysis and gluconeogenesis by the liver and
renal medulla. Postprandially, the glucose load elicits a rise in insulin and fall in glucagon,
leading to a reversal of these processes. Insulin, an anabolic hormone, promotes the storage of
carbohydrate and fat and protein synthesis.
The major portion of postprandial glucose is utilized by skeletal muscle, an effect of insulin-
stimulated glucose uptake. Other tissues, most notably the brain, utilize glucose in an insulin-
independent fashion.
PATHOGENESIS of TYPE 2 DIABETES MELLITUS
Insulin resistance and abnormal insulin secretion are central to the development of type 2 DM.
Insulin resistance precedes an insulin secretory defect but that diabetes develops only when
insulin secretion becomes inadequate.
Genetic Considerations Type 2 DM has a strong genetic component. The concordance of type 2
DM in identical twins is between 70 and 90%.
Individuals with a parent with type 2 DM have an increased risk of diabetes; if both parents have
type 2 DM, the risk approaches 40%.
Insulin resistance, as demonstrated by reduced glucose utilization in skeletal muscle, is present in
many nondiabetic, firstdegree relatives of individuals with type 2 DM.
The disease is polygenic and multifactorial, since in addition to genetic susceptibility,
environmental factors (such as obesity, nutrition, and physical activity) modulate the phenotype.
The genes that predispose to type 2 DM are incompletely identified, but recent genome-wide
association studies have identified a large number of genes that convey a relatively small risk for
type 2 DM (>20 genes, each with a relative risk of 1.06–1.5). Most prominent is a variant of the
transcription factor 7–like 2 gene that has been associated with type 2 diabetes in several
populations and with impaired glucose tolerance in one population at high risk for diabetes.
Genetic polymorphisms associated with type 2 diabetes have also been found in the genes
encoding the peroxisome proliferators–activated receptor- , inward rectifying potassium channel,
zinc transporter, IRS, and calpain 10. The mechanisms by which these genetic loci increase the
susceptibility to type 2 diabetes are not clear, but most are predicted to alter islet function or
development or insulin secretion. While the genetic susceptibility to type 2 diabetes is under
active investigation (estimation that <10% of genetic risk is determined by loci identified thus
far), it is currently not possible to use a combination of known genetic loci to predict type 2
diabetes.
PATHOPHYSIOLOGY
Type 2 DM is characterized by impaired insulin secretion, insulin resistance, excessive hepatic
glucose production, and abnormal fat metabolism.
Obesity, particularly visceral or central (as evidenced by the hip-waist ratio), is very common in
type 2 DM (80% or more are obese).
In the early stages of the disorder, glucose tolerance remains near-normal, despite insulin
resistance, because the pancreatic beta cells compensate by increasing insulin output . As insulin
resistance and compensatory hyperinsulinemia progress, the pancreatic islets in certain
individuals are unable to sustain the hyperinsulinemic state
IGT(impaired glucose tolerance ) characterized by elevations in postprandial glucose, then
develops. A further decline in insulin secretion and an increase in hepatic glucose production
lead to overt diabetes with fasting hyperglycemia. Ultimately, beta cell failure ensues.
METABOLIC ABNORMALITIES
Abnormal Muscle and Fat Metabolism
Insulin resistance, the decreased ability of insulin to act effectively on target tissues (especially
muscle, liver, and fat), is a prominent feature of type 2 DM and results from a combination of
genetic susceptibility and obesity.
Insulin resistance impairs glucose utilization by insulin-sensitive tissues and increases hepatic
glucose output; both effects contribute to the hyperglycemia. Increased hepatic glucose output
predominantly accounts for increased FPG levels, whereas decreased peripheral glucose usage
results in postprandial
hyperglycemia. In skeletal muscle, there is a greater impairment in nonoxidative glucose usage
(glycogen formation) than in
oxidative glucose metabolism through glycolysis.
Glucose metabolism in insulin-independent tissues is not altered in type 2 DM.
"Postreceptor" defects in insulin-regulated phosphorylation/dephosphorylation appear to play the
predominant role in insulin resistance.
The obesity accompanying type 2 DM, particularly in a central or visceral location, is thought to
be part of the pathogenic process. The increased adipocyte mass leads to increased levels of
circulating free fatty acids and other fat cell products
Adipocytes secrete a number of biologic products (nonesterified free fatty acids, retinol-binding
protein4, leptin, TNF- , resistin, and adiponectin).
In addition to regulating body weight, appetite, and energy expenditure, adipokines also
modulate insulin sensitivity. The increased production of free fatty acids and some adipokines
may cause insulin resistance in skeletal muscle and liver.
Free fatty acids impair glucose utilization in skeletal muscle, promote glucose production by the
liver, and impair beta cell function. In contrast, the production by adipocytes of adiponectin, an
insulinsensitizing peptide, is reduced in obesity, and this may contribute to hepatic insulin
resistance.
Adipocyte products and adipokines also produce an inflammatory state and may explain why
markers of inflammation such as IL-6 and C-reactive protein are often elevated in type 2 DM.
Inflammatory cells have been found infiltrating adipose tissue. Inhibition of inflammatory
signaling pathways such as the nuclear factor B (NF- B) pathway appears to reduce insulin
resistance and improve hyper-glycemia in animal models.
Impaired Insulin Secretion
Insulin secretion and sensitivity are interrelated .In type 2 DM, insulin secretion initially
increases in response to insulin resistance to maintain normal glucose tolerance. Initially, the
insulin secretory defect is mild and selectively involves glucose-stimulated insulin secretion. The
response to other nonglucose secretagogues, such as arginine, is preserved.
Eventually, the insulin secretory defect progresses to a state of inadequate insulin secretion.
The reason(s) for the decline in insulin secretory capacity in type 2 DM is unclear. The
assumption is that a second genetic defect—superimposed upon insulin resistance—leads to beta
cell failure. Beta cell mass is decreased by approximately 50% in individuals with long-standing
type 2 diabetes. Islet amyloid polypeptide or amylin is co-secreted by the beta cell and forms the
amyloid fibrillar deposit found in the islets of individuals with long-standing type 2 DM.
Whether such islet amyloid deposits are a primary or secondary event is not known.
The metabolic environment of diabetes may also negatively impact islet function, chronic
hyperglycemia paradoxically impairs islet function ("glucose toxicity") and leads to a worsening
of hyperglycemia. Improvement in glycemic control is often associated with improved islet
function. In addition, elevation of free fatty acid levels ("lipotoxicity") and dietary fat may also
worsen islet function.
Increased Hepatic Glucose and Lipid Production
In type 2 DM, insulin resistance in the liver reflects the failure of hyperinsulinemia to suppress
gluconeogenesis, which results in fasting hyperglycemia and decreased glycogen storage by the
liver in the postprandial state.
Increased hepatic glucose production occurs early in the course of diabetes, though likely after
the onset of insulin secretory abnormalities and insulin resistance in skeletal muscle.
As a result of insulin resistance in adipose tissue, lipolysis and free fatty acid flux from
adipocytes are increased, leading to increased lipid [very low density lipoprotein (VLDL) and
triglyceride] synthesis in hepatocytes. This lipid storage or steatosis in the liver may lead to
nonalcoholic fatty liver disease and abnormal liver function tests.
This is also responsible for the dyslipidemia found in type 2 DM [elevated triglycerides, reduced
high-density lipoprotein (HDL), and increased small dense low-density lipoprotein (LDL)
particles].
INSULIN RESISTANCE SYNDROMES
The insulin resistance condition comprises a spectrum of disorders, with hyperglycemia
representing one of the most readily diagnosed features. The metabolic syndrome, the insulin
resistance syndrome, or syndrome X are terms used to describe a constellation of metabolic
derangements that includes insulin resistance, hypertension, dyslipidemia (decreased HDL and
elevated triglycerides), central or visceral obesity, type 2 diabetes or IGT/IFG, and accelerated
cardiovascular disease.
Clinical Identification of the Metabolic Syndrome—Any Three Risk Factors
Risk Factor Defining Level
Abdominal obesity Men (waist circumference) >102 cm, Women >88 cm
Triglycerides >1.7 mmol/L (>150 mg/dL)
HDL cho-lesterol Men <1 mmol/L (<40 mg/dL) Women <1.3 mmol/L (<50 mg/dL)
Blood pressure 130/ 85 mmHg
Fasting glucose >6.1 mmol/L (>110 mg/dL)
Overweight and obesity are associated with insulin resistance and the metabolic syndrome.
However, the presence of abdominal obesity is more highly correlated with the metabolic risk
factors than is an elevated body mass index (BMI). Therefore, the simple measure of waist
circumference is recommended to identify the BMI component of the metabolic syndrome.
Two distinct syndromes of severe insulin resistance have been described in adults
Type A, which affects young women and is characterized by severe hyperinsulinemia, obesity,
and features of hyperandrogenism-- have an undefined defect in the insulin-signaling pathway.
Type B, which affects middleaged women and is characterized by severe hyperinsulinemia,
features of hyperandrogenism, and autoimmune disorders --have autoantibodies directed at the
insulin receptor. These receptor autoantibodies may block insulin binding or may stimulate the
insulin receptor, leading to intermittent hypoglycemia.
Polycystic ovary syndrome (PCOS) is a common disorder that affects premenopausal women
and is characterized by chronic anovulation and hyperandrogenism. Insulin resistance is seen in a
significant subset of women with PCOS, and the disorder substantially increases the risk for type
2 DM, independent of the effects of obesity.
ACUTE COMPLICATIONS OF DM
Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are acute
complications of diabetes.
DKA was formerly considered a hallmark of type 1 DM, but also occurs in individuals who lack
immunologic features of type 1 DM and who can sometimes subsequently be treated with oral
glucose-lowering agents. The initial management of DKA is similar.
HHS is primarily seen in individuals with type 2 DM.
Both disorders are associated with absolute or relative insulin deficiency, volume depletion, and
acid-base abnormalities.
Chronic Complications of Diabetes Mellitus
Microvascular
Eye disease
Retinopathy (nonproliferative/proliferative)
Macular edema
Neuropathy
Sensory and motor (mono- and polyneuropathy)
Autonomic
Nephropathy
Macrovascular
Coronary heart disease
Peripheral arterial disease
Cerebrovascular disease
Other
Gastrointestinal (gastroparesis, diarrhea)
Genitourinary (uropathy/sexual dysfunction)
Dermatologic
Infectious
Cataracts
Glaucoma
Periodontal disease
Hearing loss
The risk of chronic complications increases as a function of the duration and degree of
hyperglycemia; they usually do not become apparent until the second decade of hyperglycemia.
Since type 2 DM often has a long asymptomatic period of hyperglycemia, many individuals with
type 2 DM have complications at the time of diagnosis.
The microvascular complications of both type 1 and type 2 DM result from chronic
hyperglycemia. Large, randomized clinical trials of individuals with type 1 or type 2 DM have
conclusively demonstrated that a reduction in chronic hyperglycemia prevents or delays
retinopathy, neuropathy, and nephropathy. Other incompletely defined factors may modulate the
development of complications. For example, despite long-standing DM, some individuals never
develop nephropathy or retinopathy. Many of these patients have glycemic control that is
indistinguishable from those who develop microvascular complications, suggesting that there is a
genetic susceptibility for developing particular complications.
Evidence implicating a causative role for chronic hyperglycemia in the development of
macrovascular complications is less conclusive.
Coronary heart disease events and mortality rate are two to four times greater in patients with
type 2 DM. These events correlate with fasting and postprandial plasma glucose levels as well as
with the A1C. Dyslipidemia and hypertension also play important roles in macrovascular
complications.
Mechanisms of Complications
Although chronic hyperglycemia is an important etiologic factor leading to complications of
DM, the mechanism(s) by which it leads to such diverse cellular and organ dysfunction is
unknown.
At least four prominent theories, which are not mutually exclusive, have been proposed . An
emerging
hypothesis is that hyperglycemia leads to epigenetic changes in the affected cells
.
One theory is that increased intracellular glucose leads to the formation of advanced
glycosylation end products (AGEs), which bind to a cell surface receptor, via the nonenzymatic
glycosylation of intra- and extracellular proteins. Nonenzymatic glycosylation results from the
interaction of glucose with amino groups on proteins. AGEs have been shown to cross-link
proteins (e.g., collagen, extracellular matrix proteins), accelerate atherosclerosis, promote
glomerular dysfunction, reduce nitric oxide synthesis, induce endothelial dysfunction, and alter
extracellular matrix composition and structure.
The serum level of AGEs correlates with the level of glycemia, and these products accumulate as
the glomerular filtration rate (GFR) declines.
A second theory is based on the observation that hyperglycemia increases glucose metabolism
via the sorbitol pathway. Intracellular glucose is predominantly metabolized by phosphorylation
and subsequent glycolysis, but when increased, some glucose is converted to sorbitol by the
enzyme aldose reductase. Increased sorbitol concentration alters redox potential, increases
cellular osmolality, generates reactive oxygen species, and likely leads to other types of cellular
dysfunction.Testing of this theory in humans, using aldose reductase inhibitors, has not
demonstrated significant beneficial effects on clinical endpoints of retinopathy, neuropathy, or
nephropathy.
A third hypothesis proposes that hyperglycemia increases the formation of diacylglycerol
leading to activation of protein kinase C (PKC). PKC alters the transcription of genes for
fibronectin, type IV collagen, contractile proteins, and extracellular matrix proteins in endothelial
cells and neurons. Inhibitors of PKC are being studied in clinical trials.
A fourth theory proposes that hyperglycemia increases the flux through the hexosamine
pathway, which generates fructose-6- phosphate, a substrate for O-linked glycosylation and
proteoglycan production. The hexosamine pathway may alter function by glycosylation of
proteins such as endothelial nitric oxide synthase or by changes in gene expression of
transforming growth factor (TGF- ) or plasminogen activator inhibitor-1 (PAI-1).
Individuals with DM are 25 times more likely to become legally blind than individuals without
DM.
Blindness is primarily the result of progressive diabetic retinopathy and clinically significant
macular edema.
Diabetic nephropathy is the leading cause of ESRD and a leading cause of DM-related morbidity
and mortality. Both microalbuminuria and macroalbuminuria in individuals with DM are
associated with increased risk of cardiovascular disease. Individuals with diabetic nephropathy
commonly have diabetic retinopathy.
Neuropathy and Diabetes Mellitus
Diabetic neuropathy occurs in 50% of individuals with long-standing type 1 and type 2 DM. It
may manifest as polyneuropathy, mononeuropathy, and/or autonomic neuropathy.The
development of neuropathy correlates with the duration of diabetes and glycemic control.
Additional risk factors are BMI (the greater the BMI, the greater the risk of neurop-athy) and
smoking. The presence of cardiovascular disease, elevated triglycerides, and hypertension is also
associated with diabetic peripheral neuropathy. Both myelinated and unmyelinated nerve fibers
are lost.
Gastrointestinal/Genitourinary Dysfunction
Long-standing type 1 and 2 DM may affect the motility and function of gastrointestinal (GI) and
genitourinary systems. The most prominent GI symptoms are delayed gastric emptying
(gastroparesis) and altered small- and large-bowel motility (constipation or diarrhea).
Diabetic autonomic neuropathy may lead to genitourinary dysfunction including cystopathy,
erectile dysfunction, and female sexual dysfunction (reduced sexual desire, dyspareunia, reduced
vaginal lubrication). Symptoms of diabetic cystopathy begin with an inability to sense a full
bladder and a failure to void completely.
Cardiovascular Morbidity and Mortality
Cardiovascular disease is increased in individuals with type 1 or type 2 DM. The Framingham
Heart Study revealed a marked increase in PAD, CHF, CHD, MI, and sudden death (risk
increase from one- to fivefold) in DM.
The American Heart Association has designated DM as a "CHD risk equivalent." Type 2
diabetes patients without a prior MI have a similar risk for coronary artery –related events as
nondiabetic individuals who have had a prior MI
PREVENTION
Impaired glucose tolerance and impaired fasting glucose form an intermediate stage in the natural
history of diabetes mellitus.Impaired glucose tolerance is defined as two-hour glucose levels of
140 to 199 mg per dL (7.8 to 11.0 mmol) on the 75-g oral glucose tolerance test, and impaired
fasting glucose is defined as glucose levels of 100 to 125 mg per dL (5.6 to 6.9 mmol per L) in
fasting patients.
Classification of glucose tolerance state
State FPG level (mg/dl)2-h plasma glucose in OGTT (mg/dl)*
IFG 100–125 <200
Isolated IFG
100–125 <140
IGT <126 140–199
Isolated IGT
<100 140–199
Combined IFG/IGT 100–125 140–199
State FPG level (mg/dl)2-h plasma glucose in OGTT (mg/dl)*
NGT <100 <140
These glucose levels are above normal but below the level that is diagnostic for diabetes. Patients
with impaired glucose tolerance or impaired fasting glucose have a significant risk of developing
diabetes and thus are an important target group for primary prevention
In an analysis of six prospective studies,6 the risk of developing diabetes was found to be approximately
3.6 to 8.7 percent per year in patients with IGT. During the pre-diabetic state, the risk of a CVD
event is modestly increased (11–22)
IFG and IGT frequently are associated with metabolic syndrome. It is important for family physicians to
identify patients with metabolic syndrome and to intervene aggressively to reduce the risk of diabetes
and macrovascular disease.
People with isolated IFG predominantly have hepatic insulin resistance and normal muscle
insulin sensitivity, whereas individuals with isolated IGT have normal to slightly reduced
hepatic insulin sensitivity and moderate to severe muscle insulin resistance.
People with isolated IFG have a decrease in first-phase (0–10 min) insulin secretory
response to intravenous glucose and a reduced earlyphase (first 30 min) insulin response to
oral glucose. However, the late-phase (60–120 min) plasma insulin response during the
OGTT is normal in isolated IFG. Isolated IGT also has a defect in early-phase insulin
secretion in response to an oral glucose load and in addition has a severe deficit in
latephase insulin secretion.
In IFG the impairment in early insulin response in combination with hepatic insulin resistance
results in the excessive early rise of plasma glucose in the 1st hour of the OGTT. However, the
preservation of late insulin secretion combined with normal muscle insulin sensitivity allows
glucose levels to return to the preload value in isolated IFG.
In contrast, in isolated IGT the defective late insulin secretion, combined with muscle and
hepatic insulin resistance, results in prolonged hyperglycemia after a glucose load.
The majority of people with IFG/IGT will develop progressive hyperglycemia and eventually
meet criteria for diabetes.
A wide variety of interventions have been shown to alter the natural history of IFG/IGT
progression to diabetes.
The prevention or delay of diabetes should lead to a decrease in duration-dependent
diabetesrelated microvascular complications; however, direct data are not available to determine
whether this occurs. Published trials have not been sufficiently powered to show a reduction in
these hard outcomes.
One of the other major reasons to recommend therapeutic interventions for individuals with
IFG/IGT is the potential
to reduce the long-term increased risk of CVD associated with diabetes.
The epidemic increase in diabetes and its serious long-term consequences strongly support
efforts to prevent its occurrence, with the expectation that morbidity and mortality will be
decreased.
The strong association between diabetes and obesity suggests that our first priority is
maintenance of healthy weight
and obesity prevention. All individuals who are overweight or obese, regardless of their blood
glucose value, should be intensively counseled to lose weight and to exercise. lifestyle
modification therapy emphasizing modest weight loss (5–10% of body wt) and moderate-
intensity physical activity (_30 min daily) is the treatment of choice for individuals with
IFG/IGT. it seems very likely that lifestyle modification would benefit all people with IFG/IGT
The population to be screened for IFG/IGT should be the same as currently recommended for
screening for diabetes.
At present, FPG and 2-h OGTT are the tests of choice to identify all states of hyperglycemia
Type 2 DM is preceded by a period of IGT or IFG, and a number of lifestyle modifications and
pharmacologic agents prevent or delay the onset of DM.
The Diabetes Prevention Program (DPP) demonstrated that intensive changes in lifestyle (diet
and exercise for 30 min/d five times/week) in individuals with IGT prevented or delayed the
development of type 2 DM by 58% compared to placebo.
This effect was seen in individuals regardless of age, sex, or ethnic group.
In the same study, metformin prevented or delayed diabetes by 31% compared to placebo.
The lifestyle intervention group lost 5–7% of their body weight during the 3 years of the study.
Studies in Finnish and Chinese populations noted similar efficacy of diet and exercise in
preventing or delaying type 2 DM; -glucosidase inhibitors, metformin, thiazolidinediones, and
orlistat prevent or delay type 2 DM but are not approved for this purpose.
Individuals with a strong family history of type 2 DM and individuals with IFG or IGT should be
strongly encouraged to maintain a normal BMI and engage in regular physical activity.
Pharmacologic therapy for individuals with prediabetes is currently controversial because its
cost-effectiveness and safety profile are not known.
The ADA has suggested that metformin be considered in individuals with both IFG and IGT who
are at very high risk for progression to diabetes (age <60 years, BMI 35 kg/m2, family history of
diabetes in first-degree relative, elevated triglycerides, reduced HDL, hypertension, or A1C
>6.0%).
Individuals with IFG, IGT, or an A1C of 5.7–6.4% should be monitored annually to determine if
diagnostic criteria for diabetes are present.
Author/date Aim of study Type of the study
Main findings/conclusion
Strengths and limitations
Knowler et al., (2002)
To assess the effectiveness of intensive lifestyle intervention (The US diabetes prevention program) in prevention of diabetes
Randomized control trial
Significantly lower incidence of diabetes cases and higher leisure time physical activity in the intervention group after an average of 2.8 years follow up. There was a significant
reduction in fasting
plasma glucose in the
intervention group
during 2.8 years follow
up.
Representative sample Good sample size (3234) Partly blinded study Unclear process of follow up including the number of participants who dropped out Exercises were
assessed by self-
reported
questionnaire.
Diabetes Prevention Program Research Group et al., (2009)
To assess the effectiveness of intensive lifestyle intervention (The US diabetes prevention program) against general lifestyle recommendations in prevention of diabetes
Cohort study After 10 years follow up, the incidence rate did not differ significantly between the lifestyle intervention and the control group. However, the cumulative incidence rate (overall new diabetes cases over 10 years) of diabetes was the least in lifestyle intervention
This study was designed similar to (Knowler et al., 2002), but the follow up period was extended to 10 years. Possibility of other
confounding factors
as a result of long
follow up period
Allen et al., (2008)
To evaluate lifestyle intervention to prevent type 2 diabetes among American Indian
Randomized control trial
The mean change of fasting blood glucose was significantly reduced among participants after
Small sample size (42) Less prone to selection bias Exercise were
women with impaired glucose tolerance
6, 12 and 18 months follow up.
assessed by self-
reported
questionnaire
Thompson et al., (2008)
To evaluate lifestyle intervention to prevent type 2 diabetes among American Indian women with impaired glucose tolerance
Randomized control trial
No significant change in the mean of fasting blood glucose among participants during 6, 12 and 18 months follow up
A sample size of 200 Participants were randomized by tow computer generated lists Less prone to
selection bias
Yates et al., (2009)
To evaluate the effectiveness of (PREPARE) program, which promote walking activity with or without pedometer, in improving impaired glucose tolerance
Randomized control trial
A structured education program with pedometer use (PREPARE) is effective in reducing fasting plasma glucose and 2 h glucose after one year follow up.
Small sample size (87) More men than women participated Partly blinded study Short follow up period Clear process of
randomization
Tuomilehto et al., (2001)
To assess the effect of exercise and dietary life style intervention (The Finnish diabetes prevention program) in preventing type 2 diabetes for people who are at risk.
Randomized control trial
The Finnish diabetes prevention program showed significant reduction in fasting plasma glucose and 2 h plasma glucose among the intervention group after one year follow up
Sample size of (523) Clear process of randomization Partly blinded study Exercise was assessed only by self-reported questionnaire
Ramachandran et al., (2006)
To assess the effectiveness of lifestyle intervention in reducing diabetes cases among Asian Indians with
Randomized control trial
The cumulative incidence of diabetes was significantly lower in the intervention groups
Sample size of (531) Unclear process of randomization Blinding was not achieved More men (412)
than women (110)
impaired glucose tolerance.
participated in the
study
AIMS AND OBJECTIVES
Improvement in glycemic control in patients with IFG and IGT in overweight (BMI> 25) and obese individuals with weight reduction and exercise
MATERIALS AND METHODS
This study was conducted in outpatient based clinic in Hyderabad during the period from
December 2011 to may 2012 over a period of 6 months ,consecutive patients present with
impaired fasting glucose were enrolled for the study with their prior permission after explaining
the details fully.
METHODOLOGY
A)INCLUSION CRITERIA
1)people with BMI> 25
2)Age > 30yrs
3)Fasting plasma glucose > 100mg/dl and <126mg/dl
4)2-hr plasma glucose >140mg/dl and <200mg/dl in OGTT-oral glucose tolerance test
B)EXCLUSION CRITERIA
1)Prior history of diabetes mellitus
2)Who on metformin theraphy for other reasons
CLINICAL DATA –around 25 individuals enrolled in this study with prior permission from
them . In all of them I measured body weight, height ,BMI, checked Blood pressure. Regular
plasma fasting glucose, fasting lipids measured. OGTT performed and 2hr plasma glucose
recorded. I advised them regular exercise of 30-45mts a day for minimum five days a week.
Fasting glucose measured after minimum of 8 hours fast
OGTT performed with 75 gms of oral glucose and 2 hr post bood glucose recorded
LIPID PROFILE measured after minimum of 12 hours fast
Statistical analysis For quantitative data , mean , standard deviation used to compare two
groups, responders, progressors.,obese, overweight. Z-test was applied to compare two
proportions.chisquare test or fisher’ test to compare outcomes between two groups.
Abbreviations used
HT - height in cms
WT -1 - weight in kilograms base line reading.
WT -2 - weight in kilograms after 6 months
BMI - body mass index kg/cm2
W.C.-1 waist circumference in cms base line reading
W.C.-2 waist circumference in cms after 6 months
SYS BP-1 systolic blood pressure in mm hg base line reading
SYS BP-2 systolic blood pressure in mm hg after 6 months
DIA BP-1 diastolic blood pressure in mm hg base line reading
DIA BP -2 - diastolic blood pressure in mm hg after 6 months
FG-1 - fasting glucose in mg/dl base line reading
FG-2 fasting glucose in mg/dl after 6 months
OGTT-1 oral glucose tolerance test in mg/dl base line reading
OGTT-2 oral glucose tolerance test in mg/dl after six months.
HDL-1 - high density lipoproteins in mg/dl base line reading
HDL-2 – high density lipoproteins in mg/dl after 6 months
LDL-1 – low density lipoproteins in mg/dl base line reading
LDL-2 – low density lipoproteins in mg/dl after 6 months
TG-1 - triglycerides in mg/dl base line reading
TG-2 - triglycerides in mg/dl after 6 months
Responders – who responded positively after 6 months whose blood sugars reduced
Progressors - who do not responded positively after 6 months , whose blood sugars continue to
raise.
RESULTS
The study was conducted in 25 patients over a period of 6 months.
Total no of patients - 25
Total no of males - 15
Total no of females - 10
No of persons with Impaired Fasting glucose (IFG) – 25
No of persons with Impaired Glucose Tolerance (IGT)- 20
No of overweight persons - 19 (76%)
No of obese persons -6 (24%)
No of persons who improved glucose control with exercise and wt reduction -19 (76%)
No of persons who progressed with increasing glucose levels -6 (24%)
No of obese persons who showed positive response 2 out of 6----- 33.33%
No of overweight persons who showed positive response 16 out of 19---84%
No of persons who reduced their weight is -21
No of persons who maintained or increased their weight is -- 04
Mean weight initially is 75.67 kg
Mean weight after 6 months is 72.28 kg a change of 4.41%
Mean weight in overweight persons is 73.20 kg after 6 months 69.89 kg a change of 4.5%
Mean weight in obese persons is 83.5 kg after 6 months 80.00 kg cnahge of 4.1 %
Mean weight in responders is 75.04 kg after 6 months 71 kg decrease by 5.3 %
Mean weight in progressors is 77.66 kg after 6 months 76.33 kg decrease by 1.71 %
1 out of 4 persons who doesnot lost weight responded positively.
Mean waist circumference in males – 89.46 cms
After 6 months -- 86.66 cms - 3.12% change
Mean waist circumference in females—84.2 cms
After 6 months --- 81.4 cms -3.32 % change
Mean Fasting Glucose -1in all the patients is ---114.56
Mean Fasting Glucose -2 in all the patients is ---108.4---change of 5.37 %
Mean OGTT-1 all the patients is --- 160.32
Mean OGTT -2 in all the patients is--- 150.64---- CHANGE of 6.03%
Mean fasting glucose in responders is – 114.05—after 6 months - 102.20 decreased by (10.39%)
Mean fasting glucose in progressors is – 116.16- after 6 months - 128.00 increased by (10.19%)
Mean OGTT values in responders is -158.94 after 6 months - 140.63 decreased by (11.52%)
Mean OGTT values in progressors is 164.66 after 6 months 182.33 increased by ( 10.73 %)
No of persons with normal BP -05
No of persons with prehypertension -13
No of persons with stage 1 hypertension -07
No of persons stage 11 hypertension -00
Systolic BP reduced in 3 out of 19 responders significantly with exercise.
No change in BP observed in 15 out of 19 responders.
1 out of 6 obese persons showed decreased systolic BP after exercise.
2 out of 19 over weight persons showed improvement in systolic BP.
Systolic BP increased in 1 out of 19 responders.
Systolic BP- no significant change observed in progressors.
16 out of 19 reponders showed mild increase in HDL levels after exercise.
6 out of 6 progressors showed moderate increase in HDL level after exercise.
10 out of 19 responders showed a significant decrese in LDL level after exercise.
7 out of 19 responders showed almost no change in LDL level after exercise.
2 out of 19 responders showed increase in LDL level after exercise.
3 out of 6 progressors showed a significant decrease in LDL level after exercise.remaining 3 showed
almost the same values.
12 out of 19 responders showed a moderate decrease in TG level after exercise.remaing have almost the
same values.
3 out of 6 progressors showed moderate decrease in the TG values after exercise. 2 showed no
significant difference .1 out of 6 showed a moderate increase in TG levels.
AGE DISTRIBUTION OF PATIENTS
AGE in Yrs MALE FEMALE RESPONDERS PROGRESSORS TOTAL
31-40 08 06 14 00 14
41-50 06 03 04 05 09
51-60 01 01 01 01 02
TypeMean wt-1 KG
MeanWt-2KG
Mean W.C.-1cms
MeanW.C.-2cms
MeanFG-1Mg/dl
MeanFG-2Mg/dl
Mean OGTT-1Mg/dl
Mean OGTT-2Mg/dl
Mean BMIKg/m2
Responders
75.04 71.00 86.89 84.47 114.05 102.21 158.94 140.63 28.05
Progressors 77.66 76.33 88.83 84.83 116.16 126.83 164.66 182.33 28.95
total
male
female
overw
eight
obese
responders
progre
ssors
weight r
educed
weight n
ot red
uced0
5
10
15
20
25
3025
15
10
19
6
19
6
21
4
Series1
Gender distribution of patients
total responders progressors0
2
4
6
8
10
12
14
16
malesfemales
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
FG-1
106
110
109
120
109
122
120
111
108
115
120
115
109
107
114
118
120
115
119
FG-2
101
105
100
101
98 100
121
100
96 99 105
102
105
97 104
97 108
98 105
10
30
50
70
90
110
130
FG changes in responders
glu
cose
mg/
dl
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
OGTT-1
155
160
136
145
178
165
134
156
178
180
167
154
139
136
178
169
166
154
170
OGTT-2
140
150
123
135
160
135
132
138
139
144
140
145
123
130
151
142
146
138
161
10
50
90
130
170
OGTT values in responders G
luco
se m
g/d
l
Weight changes in responders
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
WT in kg I
71 66.3
77 75 88 82 75 76 61.5
84.5
79 85 62 74 73 74 73 67 82.5
WT in KG 2
67 67 73 71 83 77 71 72 57 79 75 80 58 70 69 71 70 61 78
525456585
weight changes in responders
weig
ht
in k
gs
1 2 3 4 5 6
Series1 69 63 81 74 90 89
Series2 66 65 81 70 90 86
5152535455565758595
weight changes in progressorsw
eigh
t in
kgs
1 2 3 4 5 6
FG-1 111 105 118 124 117 122
FG-2 128 122 130 130 127 131
10
30
50
70
90
110
130
FG changes in progressors
bloo
d gl
ucos
e m
g/dl
1 2 3 4 5 6
OGTT-1 180 148 154 133 188 185
OGTT-2 200 156 206 130 198 204
25
75
125
175
225
OGTT changes in progressorsb
llod
glu
cose
mg/
dl
DISCUSSION
Out of the 25 cases of Impaired Fasting glucose and Impaired Glucose Tolerance studied at
outpatient based clinic during the period from December 2011 to may 2012 , most of the
recognized risk factors were seen.
The study showed that IFG & IGT improve with exercise and weight gain.
The mean age in our study is 41.04 yrs.
The p value between different age groups in relation to glucose improvement is variable,
significant between 31-40yrs & 41-50 yrs , but not significant when 31-40 yrs& and 51-60 yrs
groups compared.
The males and females ratio is 3:2 – 15 and 10
12 out of 15 males responded positively and 7 out of 10 females responded positively. Sex
difference has no significant impact on the improvement in IFG & IGT status ( p value 0.65)
Over weight patients are 19 out of which 17 responded positively.
Obese patients are 06 out of which 02 responded positively.
There a significant relation between overweight and obese patients in reducing glucose levels.
IFG and IGT improve more in Overweight patients compared to obese patients ( p value 0.015)
Out of 25 patients 21 patients loose weight after 6 months and 4 patients not loose weight.
Those who lost weight showed a significant improvement in glycemic status compared to those
who did not loose weight. ( p value 0.03)
FACTORS INFLUENCING OUTCOME IN RESPONDERS AND PROGRESSORS
Characteristic Total Glucose reduced Glucose not reduced
P value
Sex
Male
Female
15
10
12
07
03
03
0.65
NOT SIGNIFICANT
Weight
Overweight
Obese
19
6
17
02
02
04
0.015
SIGNIFICANT
Weight
Wt reduced
Wt not reduced
21
4
18
01
03
03
0.03
SIGNIFICANT
Glucose
IFG
IFG& IGT
25
20
19
15
06
05
1
NOT SIGNIFICANT
Age in yrs
31-40
41-50
31-40
14
09
14
14
04
14
00
05
00
0.003
Significant
0.12
51-60 02 01 01 Not significant
CONCLUSIONS
1.There is a significant reduction in blood glucose values with exercise and weight reduction in patients with Impaired Fasting Glucose and Impaired Glucose tolerance.
2.Exercise and weight reduction a minimum of 5% is advised to patients with Impaired Fasting Glucose and Impaired Glucose Tolerance to prevent or to delay progression to Type 2 Diabetes Mellitus.
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