Impaired Glucose Tolerance Subjects Research Articles

Characteristics of the daily blood glucose profiles of impaired glucose tolerance and type 2 diabetes mellitus subjects by continuous glucose monitoring system

To investigate the characteristics of daily glucose profiles of the impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) subjects by continuous glucose monitoring system (CGMS) so as to instruct the development of rational programs of treatment. The CGMS data of 6 normal glucose tolerance (NGT), 10 IGT, and 20 newly diagnosed T2DM subjects were analyzed. (1) The values of average blood glucose, standard deviation of blood glucose, total time of plasma glucose > or = 7.8 mmol/L (T(PG) > or = 7.8 mmol/L) of the T2DM subjects were all significantly higher than those of IGT subjects (all P < 0.05), and these values of the IGI subjects were all significantly higher than those of the NGT subjects (all P < 0.05). The CGMS blood glucose profile excursion were also more and more fluctuant with the deterioration of glucose tolerance. (2) In the IGT group, the time of PG reaching peak was 109 minutes +/- 32 minutes and the daily time of PG > or = 7.8 mmol/L was 3.0 hours +/- 0.8 hours. In the newly diagnosed T2DM group, the time of PG reaching peak was 92 minutes +/- 22 minutes, and the daily time of PG > or = 11.1 mmol/L was 12.6 hours +/- 1.3 hours. The blood glucose increased more quickly and more sharply, and continued for more time after breakfast. (1) CGMS data accurately display the characteristics of daily 24 h blood glucose profiles of the IGT and newly diagnosed T2DM subjects, and CGMS examination helps instruct the development of rational treatment program. (2) In daily life, the time of PG > or = 7.8 mmol/L in IGT subjects was nearly 3 hours. (3) With the deterioration of glucose tolerance, the postprandial glucose peak is elevated higher and more rapidly, and the daily blood glucose profile excursion becomes more and more fluctuant.

Urban-Rural Differences in the Prevalence of Foot Complications in South-Indian Diabetic Patients

Diabetes is recognized to be common in Asian Indians. The number of people with diabetes in the world is expected to double between 2000 and 2030. The greatest absolute increase in the number of people with diabetes will be in India (1). Regional studies from urban areas of India have shown a several-fold increase in the prevalence of diabetes in the last 2 decades (2). In a national survey reported in 2001, a concomitant increase in prevalence of impaired glucose tolerance (IGT) was noted (3). In four of six cities, the ratio of IGT to diabetes was greater than one, implying the possibility of a future conversion of IGT subjects to diabetes. An urban-rural difference in the prevalence rate was found, indicating that the environmental factors related to urbanization had a significant role in increasing the prevalence of diabetes (4). It was shown that diabetes had increased threefold over a span of 14 years in a rural population in southern India (5). The prevalence of diabetes in the urbanizing rural population was found to be midway between the rural and urban population (6). In India, diabetic foot infection is a common cause for hospital admission among diabetic patients and is caused by a number of sociocultural practices (7). The economic and emotional consequences for the patient and the family can be enormous (8). There is not much comparative data on the occurrence of foot complications between urban and rural populations. This study was therefore done in an …

Persistent impaired glucose tolerance has similar rate of risk factors as for diabetes—Results of Indian Diabetes Prevention Programme (IDPP)

Objective To determine the occurrence of persistent impaired glucose tolerance (IGT) (two times OGTT positive) and to compare the physical and clinical characteristics with subjects having transient IGT or diabetes. Research design and methods Nondiabetic subjects aged 35–55 years were screened ( n = 10,839, M:W 8667:2172) using 2 h capillary blood glucose. IGT was diagnosed in 1332 (12.3%). Among them, 1025 (77%) responded for a second OGTT and 531 subjects (51.8%) had persistent IGT. Biochemical, demographic and anthropometric characteristics were compared among the normal (NGT, 30.1%), IGT and diabetic subjects (DM, 18%) at second GTT. Results All had similar age. BMI, waist circumference and body fat percentage were lower in NGT than in IGT and diabetes. IGT and diabetes had similar characteristics. Family history of diabetes was the highest in persistent IGT. Conclusion Among the screened subjects, 1 in 20 had persistent IGT. Subject with persistent IGT had higher rates of risk factors for diabetes, such as high BMI, waist circumference and body fat percentage.

Japanese IGT Subjects with High Insulin Response Are Far More Frequently Associated with the Metabolic Syndrome Than Those with Low Insulin Response

Impaired glucose tolerance (IGT) represents a prediabetic state positioned somewhere between normal glucose tolerance and diabetes, which is also assumed to make individuals in this state highly susceptible to atherosclerotic disease. IGT also accounts for a highly heterogeneous population, with the condition varying from individual to individual. In this study, we stratified subjects with IGT by their insulin response and compare the pathology of IGT when it is associated with high or low insulin response to gain insight into the diverse pathology of IGT. Of the male corporate employees who underwent 75 g OGTT at the corporation's healthcare center, 150 individuals diagnosed with IGT (isolated IGT, combined IGT and IFG) comprised our study subjects. The study subjects were stratified into four quartiles by percentile AUC for insulin, and those in the 25th or less percentile were defined as the low insulin response group (n = 37), vs those in the 76th or greater percentile defined as the high insulin response group (n = 38), and these groups were compared. There was no significant difference observed between the two groups in regard to post-OGTT glucose response and area under the glucose curve. However, the high insulin response group was associated with higher BMI, subcutanesous fat area, uric acid levels, HOMA-beta cell values, and delta insulin/delta glucose (30 min) than the low insulin response group. The number of risk factors for the metabolic syndrome detected (as defined by the ATPIII diagnostic criteria) per subject was 2.84 +/- 0.17 and 2.08 +/- 0.20, respectively, in the high insulin response group and in the low insulin response group, with the number significantly (p < 0.05) higher in the high insulin response group. Furthermore, the incidence of the metabolic syndrome as defined by the ATPIII diagnostic criteria was 63.2% (24/38) in the high insulin response group vs 32.4% (12/27) in the low insulin response group, with the incidence significantly (p < 0.01) higher in the high insulin response group. Likewise, the incidence of the metabolic syndrome as defined by the Japanese diagnostic criteria was found to be significantly (p < 0.05) higher in the high insulin response group at 50% (19/38) compared to 27.0% (10/37) in the low insulin response group. Our study findings suggest that IGT subjects with high insulin response and those with low insulin response vary greatly in regard to the number of atherosclerotic risk factors complicated and the frequency with which they are associated with the metabolic syndrome. It is also shown in middle-aged Japanese males that of the two forms of IGT, IGT with high insulin response is more closely linked to the pathogenesis of atherosclerotic cardiovascular disease.

老年医学における未病―老年疾患の予防をどのようにすすめるか―４．糖尿病と未病

Diabetes Mellitus is thought as the presymptomatic stage to cause various vascular diseases. From the point of view that diabetes is already a disease, this paper discusses the prevention of the manifestation of diabetes in the elderly. STOP-NIDDM study demonstrated that acarbose, an alpha-glucosidase inhibitor, reduced the onset of diabetes in impaired glucose tolerance (IGT) subjects by 24%. On the other hand, the Diabetes Prevention Program (DPP) study for IGT subjects revealed that intensive life style intervention prevented diabetes most powerfully by 58% and metformin treatment also reduced by 31%. Furthermore, HOPE, LIFE, and SCOPE studies against hypertension showed that ACI or ARB reduced diabetes by 20-32%, and the WOSCOT study that pravastatin, a HMG-CoA reductase inhibitor, reduced diabetes by 30%. These accumulated results suggest that the most suitable strategy to prevent diabetes in the elderly is intensive life style intervention, and in cases incapable of exercise and diet therapy, acarbose or metformin are recommended for IGT. When associated with hypertension and/or hyperlipidemia, the subjects have to receive ACI or ARB and statins to prevent diabetes.

Short-term ingestion of Ginkgo biloba extract does not alter whole body insulin sensitivity in non-diabetic, pre-diabetic or type 2 diabetic subjects—A randomized double-blind placebo-controlled crossover study

Ingestion of Ginkgo biloba Extract (EGb 761) may increase pancreatic beta-cell function in both healthy subjects with normal glucose tolerance (NGT) as well as patients with Type 2 Diabetes mellitus (T2DM). Since hyperinsulinemia is a hallmark of T2DM, it is important to verify that increased insulin production is not due to increased insulin resistance. NGT subjects (n = 10; age, 44.2 +/- 13.9 years old), impaired glucose tolerance (IGT) (n = 8; age 51.3 +/- 6.6 years old) and T2DM subjects (n = 8, 51.6 +/- 15.2 years old) completed a randomized, double-blind, placebo-controlled crossover study. After ingesting either EGb 761 (120 mg/day as a single dose) or placebo during each 3-month arm, a 2-step euglycemic insulin clamp was performed. At the low insulin infusion rate (10 mU/m2/min) the glucose metabolic rates (M values) were 3.5 +/- 1.5 vs. 3.0 +/- 0.5 mg/kg (P = 0.16), 3.0 +/- 0.4 vs. 2.8 +/- 0.8 mg/kg (P = 0.19) and 2.6 +/- 0.7 vs. 2.4 +/- 0.5 mg/kg (P = 0.09) for the placebo and EGb 761 cycles, in the NGT, IGT and T2DM subjects, respectively. At the high insulin infusion rate (40 mU/m2/min) the M values were 7.3+/-2.3 vs. 8.1 +/- 2.5mg/kg (P = 0.07), 6.2 +/- 1.6 vs. 6.5 +/- 2.1 mg/kg (P = 0.32) and 3.6 +/- 1.6 vs. 3.5 +/- 1.0 mg/kg (P = 0.34) for placebo vs. EGb 761 cycles, in the NGT, IGT and T2DM subjects, respectively. The ingestion of 120 mg of EGb 761 as a single for 3 months did not produce insulin resistance in the non-diabetic or pre-diabetic subjects or exacerbate the disease in the T2DM subjects.

Increased plasma adiponectin in response to pioglitazone does not result from increased gene expression

Plasma levels of adiponectin are lower in obese and insulin-resistant subjects compared with lean and insulin-sensitive ones. Thiazolidinediones increase plasma adiponectin levels in diabetic subjects, although the mechanism of this increased plasma adiponectin has not been well studied. In the present study, we compared the plasma levels and adipose tissue expression of adiponectin in subjects with normal (NGT) and impaired glucose tolerance (IGT) and also studied the effects of metformin and pioglitazone on plasma and adipose tissue mRNA level of adiponectin in IGT subjects. IGT subjects had lower plasma adiponectin levels compared with NGT subjects, and similarly IGT subjects had lower adiponectin mRNA levels. In contrast, the increased plasma levels of adiponectin in response to pioglitazone were not associated with increased adiponectin expression in adipose tissue. Metformin did not cause any change in plasma or expression levels of adiponectin. Other adipokines were examined, and both pioglitazone and metformin decreased plasma levels of resistin in IGT subjects, and pioglitazone (but not metformin) decreased plasma levels of leptin. These data suggest that pioglitazone increases plasma adiponectin levels by posttranscriptional regulation in contrast to transcriptional regulation of adiponectin in relation to insulin sensitivity in NGT vs. IGT subjects.

Expression of CD68 and Macrophage Chemoattractant Protein-1 Genes in Human Adipose and Muscle Tissues

To examine the role of adipose-resident macrophages in insulin resistance, we examined the gene expression of CD68, a macrophage marker, along with macrophage chemoattractant protein-1 (MCP-1) in human subcutaneous adipose tissue using real-time RT-PCR. Both CD68 and MCP-1 mRNAs were expressed in human adipose tissue, primarily in the stromal vascular fraction. When measured in the adipose tissue from subjects with normal glucose tolerance, covering a wide range of BMI (21-51 kg/m2) and insulin sensitivity (S(I)) (0.6-8.0 x 10(-4)min(-1).microU(-1).ml(-1)), CD68 mRNA abundance, which correlated with the number of CD68-positive cells by immunohistochemistry, tended to increase with BMI but was not statistically significant. However, there was a significant inverse relation between CD68 mRNA and S(I) (r=-0.55, P=0.02). In addition, there was a strong positive relationship among adipose tissue CD68 mRNA, tumor necrosis factor-alpha (TNF-alpha) secretion in vitro (r=0.79, P<0.005), and plasma interleukin-6 (r=0.67, P < 0.005). To determine whether improving S(I) in subjects with impaired glucose tolerance (IGT) was associated with decreased CD68 expression, IGT subjects were treated for 10 weeks with pioglitazone or metformin. Pioglitazone increased S(I) by 60% and in the same subjects reduced both CD68 and MCP-1 mRNAs by >50%. Furthermore, pioglitazone resulted in a reduction in the number of CD68-positive cells in adipose tissue and reduced plasma TNF-alpha. Metformin had no effect on any of these measures. Thus, treatment with pioglitazone reduces expression of CD68 and MCP-1 in adipose tissue, apparently by reducing macrophage numbers, resulting in reduced inflammatory cytokine production and improvement in S(I).

The E23K variant in the Kir6.2 subunit of the ATP-sensitive K+ channel does not augment impaired glucose tolerance in Caribbean subjects with a family history of type 2 diabetes

The E23K variant of the Kir6.2 gene has been shown to be associated with type 2 diabetes mellitus in Caucasian subjects. Because offspring of type 2 diabetic patients have a genetically increased risk of developing diabetes, we sought to identify the E23K variant of the Kir6.2 gene in offspring of Caribbean patients with type 2 diabetes and assess the contribution of this variant to impaired glucose tolerance in these subjects. Forty-six offspring of patients with type 2 diabetes and 39 apparently healthy subjects whose immediate parents were not diabetic ('control') were studied after an overnight fast. Anthropometric indices were measured and blood samples were collected. Fasting and 2 h plasma glucose, insulin and lipids were subsequently determined. Insulin resistance was calculated using the homeostatic model assessment technique. The offspring and control subjects had similar frequencies of the E23K polymorphism (52.6 vs 45.5%, P>0.05) and the frequency of the E23K variant did not differ significantly between gender and ethnic distributions, irrespectively of a family history of diabetes (P>0.05). There were no significant differences in biochemical risk factors for developing diabetes in offspring carriers of the E23K variant compared with offspring non-carriers of the mutation. Offspring with the E23K mutation had even significantly higher 2 h insulin concentrations when compared with control subjects. It is concluded that the presence of the Kir6.2 E23K genotype in Caribbean subjects with an immediate positive family history of diabetes does not confer significantly higher levels of biochemical risk factors for the development of type 2 diabetes.

β-Cell Function Across the Spectrum of Glucose Tolerance in Obese Youth

The profile of insulin secretion and the role of proinsulin processing across the spectrum of glucose tolerance in obese youth have not been studied. The aims of this study were to define the role of insulin secretion and proinsulin processing in glucose regulation in obese youth. We performed hyperglycemic clamps to assess insulin secretion, applying a model of glucose-stimulated insulin secretion to the glucose and C-peptide concentration data. Thirty obese youth with normal glucose tolerance (NGT), 22 with impaired glucose tolerance (IGT), and 10 with type 2 diabetes were studied. The three groups had comparable anthropometric measures and insulin sensitivity. The glucose sensitivity of first-phase secretion showed a significant stepwise decline from NGT to IGT and from IGT to type 2 diabetes. The glucose sensitivity of second-phase secretion was similar in NGT and IGT subjects yet was significantly lower in subjects with type 2 diabetes. Proinsulin-to-insulin ratios were comparable during first- and second-phase secretion between subjects with NGT and IGT and were significantly increased in type 2 diabetes. Obese youth with IGT have a significant defect in first-phase insulin secretion, while a defect in second-phase secretion and proinsulin processing is specific for type 2 diabetes in this age-group.

Contribution of impaired glucose tolerance in subjects with the metabolic syndrome: Baltimore Longitudinal Study of Aging

Background In addition to fasting plasma glucose (FPG), we examined the contribution of the oral glucose tolerance test (OGTT) in the prevalence of subjects with the metabolic syndrome (MS). Methods and Results Study participants were white adults in the Baltimore Longitudinal Study of Aging who underwent a fasting 2-hour OGTT. In men between the ages of 20 to 39, 40 to 59, 60 to 79, and 80 to 95 years, the prevalence of the MS by Adult Treatment Panel (ATP) III criteria (which excludes OGTT) was 11%, 28%, 32%, and 15%, respectively; whereas in women the prevalence was 5%, 12%, 24%, and 16%, respectively. If the current ATPIII dysglycemia criteria also included a 2-hour postchallenge glucose (2hPG) of 7.8 mmol/L or higher, the prevalence of the MS increased from 25% to 33% in men and from 15% to 21% in women ( P < .0001). In study participants with FPG less than 5.6 mmol/L, the prevalence of the MS increased from 16% to 23% in men and from 9% to 13% in women. In men between the ages of 20 to 39, 40 to 59, 60 to 79, and 80 to 95 years and FPG less than 5.6 mmol/L, the prevalence of the MS increased to 15%, 32%, 40%, and 29%, respectively ( P < .005 for men between 40 and 95 years of age), with inclusion of an abnormal 2hPG. In women between the ages of 20 to 39, 40 to 59, 60 to 79, and 80 to 95 years and FPG less than 5.6 mmol/L, the prevalence of the MS increased to 7%, 14%, 33%, and 31%, respectively, with inclusion of an abnormal 2hPG ( P < .001 for women between 60 and 95 years of age). Conclusion The prevalence of the MS is significantly underestimated when the current ATPIII criteria of FPG 6.1 mmol/L or higher is the only determinant of dysglycemia.

Acarbose in the prevention of cardiovascular disease in subjects with impaired glucose tolerance and type 2 diabetes mellitus

The prevalence of glucose intolerance is increasing dramatically worldwide. Both impaired glucose tolerance (IGT) and type 2 diabetes are associated with excess mortality from cardiovascular disease. It is now generally accepted that these cardiovascular complications are related to prevailing hyperglycemia, particularly postprandial hyperglycemia. Acarbose specifically decreases the postprandial glycemic surge in IGT and diabetic subjects. The Study To Prevent Non-insulin-dependent Diabetes Mellitus (STOP-NIDDM) trial has shown that acarbose treatment in IGT subjects decreased the risk of progression to diabetes by 36%. Furthermore, it was associated with a 49% risk reduction of cardiovascular events. In a subgroup of subjects, acarbose treatment was accompanied by a 50% decrease in the progression of intima-media thickness of the carotids. Finally, a meta-analysis of seven major studies on the use of acarbose in the treatment of diabetes indicated that acarbose treatment was associated with a 35% risk reduction of cardiovascular disease. It is proposed that the mechanism by which acarbose can lower the risk of cardiovascular events is through diminution of oxidative stress induced by postprandial glycemic excursion.

The “Good Cholesterol”

Atherosclerosis is an insidious and dangerous disease: a progressive chemical and structural injury to the blood vessels in such critical organs as the heart, brain, and kidney. The hallmark feature of atherosclerosis is the buildup of cholesterol into lesions called plaques that can reduce the flow of blood. When the delivery of blood to heart muscle drops enough, this can result in the development of chest pain or angina. Angina indicates that the heart muscle is not receiving enough oxygen to carry out its pumping functions. Atherosclerotic plaques can also suddenly rupture, develop a blood clot on their surface, and completely choke off a portion of heart muscle. This chain of events frequently results in heart attack or sudden death without warning. Atherosclerotic disease also predisposes people to stroke, peripheral vascular disease, lower-extremity amputation, and loss of kidney function, among other devastating outcomes. Despite all that we have learned in the past 50 years, atherosclerosis remains the No. 1 killer of men and women and the chief reason for loss of quality of life in Western countries. We are, however, gaining ground. Considerable research has revealed the importance of factors that increase an individual’s risk for developing this disease. Among the most important of these risk factors are elevated blood pressure, diabetes mellitus, obesity, inactivity, smoking, and cholesterol levels. When your physician measures your cholesterol level, he or she is looking at your lipid profile, which comprises low-density lipoprotein cholesterol (LDL-C, or the “bad” cholesterol), triglycerides (blood fats), and high-density lipoprotein cholesterol (HDL-C, or the “good” cholesterol). In a general way, when it comes to measurement of your LDL-C and triglyceride values, a lower value is better because these lipids drive the development and progression of atherosclerosis. In sharp contrast, when it …

Ten-year mortality and glucose tolerance status in an elderly Finnish population

The aim of this study was to determine the 10-year mortality rate of an elderly population aged 70 years or over ( n = 379) with reference to glucose tolerance status, taking into account other determinants of excess mortality. The baseline examination during 1991–1992 included a postal questionnaire, a physical examination and a 2 h OGTT, which was classified according to both the 1985 WHO criteria and the 1999 WHO criteria. Follow-up was continued until death or until 31 December 2001. 66% of men and 51% of women died within 10 years. In men, the cumulative mortalities were 84% for previously diagnosed diabetes, 67% for undiagnosed diabetes, 67% for impaired glucose tolerance (IGT) and 60% for normal glucose tolerance (NGT). The corresponding percentages for women were 76, 52, 49, and 40%. Male gender, poor self-rated health and previously diagnosed diabetes were the most powerful predictors of mortality. When adjustments were made for age, gender, BMI, cardiovascular disease, hypertension, physical exercise and self-rated health, the estimated relative mortality rate was 2.0 (95% CI 1.5–2.7) among previously diagnosed diabetic subjects, 1.3 (CI 0.8–2.2) among undiagnosed diabetic subjects and 1.1 (0.8–1.5) among IGT subjects compared to NGT subjects. These relative mortalities were higher in women than in men. When abnormal glucose tolerance was pooled into one category, the OR for excess mortality was 1.4 (95% CI 1.1–1.9).

Acute hyperglycemia alters von Willebrand factor but not the fibrinolytic system in elderly subjects with normal or impaired glucose tolerance

To assess whether acute hyperglycemia affects fibrinolytic balance in elderly subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT), 40 non-obese elderly subjects (20 NGT, age 68 +/- 8 years; and 20 IGT, age 69 +/- 11 years) were studied. On two experimental days, randomly allocated and spaced 1 week apart, plasma concentrations of glucose, insulin, fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor type 1 and von Willebrand factor (vWF) were measured in each subject at baseline (0) and 30, 60, 90, 120 min after the ingestion of 75 g glucose or a similarly sweet dose of aspartame (250 mg) (control test). In both NGT and IGT elderly subjects, tissue plasminogen activator, plasminogen activator inhibitor type 1 and fibrinogen plasma levels did not significantly change after both oral aspartame and glucose load. In IGT subjects, vWF plasmatic levels decreased after glucose (not aspartame) oral load, reaching the minimum level at 90 min after load (82.7 +/- 7.8 versus 93.7 +/- 10.2, P <0.01). These results demonstrate that acute hyperglycemia does not modify plasma fibrinolysis in elderly subjects. The decrease of plasma concentration of vWF in IGT elderly subjects requires cautious interpretation and further extensive investigations.

Possible contribution of adipocytokines on diabetic neuropathy

Neuropathy is one of the typical features of chronic complications of diabetes mellitus. Recent analyses indicate that subjects with impaired glucose tolerance (IGT) already have disturbance of peripheral nerve function. To test the role of adipocytokines, that tend to be abnormal in IGT subjects, on diabetic neuropathy, we analyzed the relationship between plasma adipocytokine levels (TNFα, adiponectin, and leptin) and nerve conduction velocity in 105 type 2 diabetic subjects (M/F = 66/39, age = 60.8 ± 11.8 years, BMI = 24.7 ± 5.0kg/m2). Adipocytokines were measured by ELISA, and motor conduction velocity (MCV) and sensory conduction velocity (SCV) in median, ulnar, and tibial nerve were measured by electrical stimulation. Motor conduction velocity and SCV were corrected by age to be 1.0 as the normal value, and the average of three nerves were used to be the representative value. Relationship between corrected MCV or corrected SCV as a dependent variable and the duration of diabetes, HbA1C, BMI, TNFα, adiponectin, and leptin concentrations as independent variables were analyzed by multiple regression. Duration of diabetes and HbA1C were highly related with both corrected MCV (P < 0.02 and P < 0.001) and SCV (P < 0.02 and P < 0.05) by this analysis. Only corrected SCV was related significantly with TNFα (P < 0.05), and close to significantly with leptin (P = 0.059) concentrations. These results indicate that increased plasma glucose levels and duration of diabetes are the major factors that modulate diabetic neuropathy. However, nerve function may be affected by plasma cytokine levels like TNFα, and this effect was more significant on sensory nerves than motor nerves. The present results suggest that adipocytokines may play a role not only on angiopathy but also on neuropathy in diabetics.

Type II Diabetes Mellitus and impaired glucose tolerance in Yemen: prevalence, associated metabolic changes and risk factors

Objective: To investigate the prevalence of type II Diabetes Mellitus (DM) and impaired glucose tolerance (IGT) and identify the metabolic abnormalities and risk factors associated with these conditions in an urban city of Yemen. Research design and methods: Cross-sectional, population-based study investigating 498 adults (245 males and 253 females) aged 25–65 years. The 1999 modified World Health Organization criteria were adopted for the diagnosis of Diabetes Mellitus and IGT. A standard questionnaire was applied and blood lipids, blood pressure, body mass index (BMI) and waist/hip ratio (WHR) were determined. Results: The overall prevalence of type II Diabetes Mellitus was 4.6% (7.4% in males and 2% in females). Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were found in 2% and 2.2% of the study population. Factors independently related to any abnormality in glucose tolerance, using logistic regression analysis, were sex, hyperlipidaemia, hypertriglyceridaemia, and hypertension; whereas sex and age related to DM. More than 80% of the type II diabetics were over the age of 40, 35% being hyperlipidaemic, 22% being hypertensive and 18% obese. Sixty percent of IGT subjects were hyperlipidaemic and 20% were obese. Approximately 78% of obese individuals (≥30 kg/m 2) had normal glucose tolerance. Conclusion: The prevalence of type II DM and its potential increase reflected by the high prevalence of obesity in normal glucose tolerance subjects in the Yemeni population constitutes a major public health problem.

C825T Polymorphism of the G Protein β3 Subunit Is Associated with Obesity but Not with Insulin Sensitivity

The common C825T polymorphism of the gene that encodes the G protein beta3 subunit has been shown to influence lipolysis in human adipocytes and to be associated with hypertension, body fat distribution, and obesity. In addition, it has been shown to be associated with insulin resistance in a small group of hypertensive subjects. We investigated whether this polymorphism contributed to the variability in obesity in our population from southern Germany and whether it was associated with insulin sensitivity of lipolysis and/or glucose disposal. We determined percentage body fat, body fat distribution, glucose tolerance [oral glucose-tolerance test (OGTT)], insulin sensitivity, and serum free fatty acids using data from OGTTs (N = 774) and clamp (euglycemic hyperinsulinemic clamp, N = 216) in normal and impaired glucose tolerant subjects who were genotyped for this polymorphism. Compared with noncarriers of the C825T mutation, subjects with the C825T variant (prevalence approximately 32%) had higher percentage body fat (p = 0.02) and higher BMI (p = 0.03). No conclusive effect was seen on serum free fatty acids measured either during fasting or at the end of a 2-hour OGTT. Insulin sensitivity determined during the OGTT and during the clamp, both adjusted for age, gender, and percentage body fat, was not different between the genotypes (p = 0.33 and p = 0.48, respectively). We have concluded that the C825T polymorphism in the G protein beta3 subunit played an important role in the determination of obesity in this German population. However, it probably had no direct effects on insulin sensitivity of lipolysis and glucose disposal.

Genetic Factors and Insulin Secretion

IGFs are important regulators of pancreatic beta-cell development, growth, and maintenance. Mutations in the IGF genes have been found to be associated with type 2 diabetes, myocardial infarction, birth weight, and obesity. These associations could result from changes in insulin secretion. We have analyzed glucose-stimulated insulin secretion using hyperglycemic clamps in carriers of a CA repeat in the IGF-I promoter and an ApaI polymorphism in the IGF-II gene. Normal and impaired glucose-tolerant subjects (n = 237) were independently recruited from three different populations in the Netherlands and Germany to allow independent replication of associations. Both first- and second-phase insulin secretion were not significantly different between the various IGF-I or IGF-II genotypes. Remarkably, noncarriers of the IGF-I CA repeat allele had both a reduced insulin sensitivity index (ISI) and disposition index (DI), suggesting an altered balance between insulin secretion and insulin action. Other diabetes-related parameters were not significantly different for both the IGF-I and IGF-II gene variant. We conclude that gene variants in the IGF-I and IGF-II genes are not associated with detectable variations in glucose-stimulated insulin secretion in these three independent populations. Further studies are needed to examine the exact contributions of the IGF-I CA repeat alleles to variations in ISI and DI.

Análisis de las alteraciones del metabolismo hidrocarbonado en la población adulta de Yecla (Murcia)

To determine the prevalence of impaired fasting glucose (IFG or GBA), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM2) in the adult population of Yecla. RESEARCH, DESIGN, AND METHODS: We performed a population-based cross-sectional study (on Primary Care Field) with stratified and random sampling (393) from 17 500 residents in Yecla with sanitary card and aged > or =30 years. We studied 286 subjects (107 declining to participate) and 261 of them (125 men and 136 women) underwent an oral glucose tolerance test (OGTT). World Health Organization (WHO-99) and American Diabetes Association (ADA-97) criteria were used for diagnosis of unknown DM2, GBA and IGT. Socio-demographic and anthropometric variables were measured. Plasma lipid, glycosylated haemoglobin (HbA1C), microalbuminuria and insulin levels also were measured. Insulin resistance was evaluated by the HOMA method. According ADA-97 criteria the prevalence of DM2 and GBA was 2.65 (CI+/-1.95) and 4.3% (+/-2.5) respectively. Underwent an OGTT, the age-adjusted prevalence of DM2, IGT and GBA (using the Spanish population of July 02) was 6.7 (95%CI, 3,7-9,7); 13.2 (95%CI, 9.1-17.3) and 0.2% (95%CI, 0-1.8) respectively. The known DM2 was 5,9% (95%CI, 3.8-8) and the global prevalence of DM2 was 12.6% (95%CI, 9.6-15.6). The diabetes was associated with overweight, overage and higher insulin, HbA1C and insulin resistance levels. There is a high prevalence of DM2 in Yecla (known/unknown 0.87/1). The ADA97 criteria only detected 53% of the unknown DM2. The 78% of normoglycemics subjects had overweight or upper-body fat distribution and diabetics people had higher BMI (Body Mass Index), Hypertension, insulinemia, HbA1C and insulin resistance levels than normoglycemics and IGT subjects.