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Query: UMLS:C0028754 (obesity)
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The effects of insulin and insulin-like growth factor I (IFG-I) on protein synthesis were compared in muscle isolated from lean and goldthioglucose (GTG)-obese mice. Two types of skeletal muscles, the red soleus and the white extensor digitorum longus (EDL) muscles, were studied. In muscles from lean mice, 6.7 nM insulin and 50 nM IGF-I caused a similar maximal stimulation of tyrosine incorporation in total proteins (40% increase). However, the potency of IGF-I was only 5-10% that of insulin both in soleus and in EDL muscles (EC50 approximately equal to 6 nM for IGF-I and 0.5 nM for insulin). Basal rate of protein synthesis was identical in muscles from GTG-obese and lean mice. Similarly, a comparable increase in the rate of protein synthesis was obtained using maximally effective concentrations of insulin and IGF-I in both lean and GTG-obese animals. SDS-polyacrylamide gel electrophoresis analysis of proteins labeled with 35S-methionine confirmed that, in muscles from lean and GTG-obese animals, insulin and IGF-I increased overall protein synthesis in a similar manner. These results suggest that the protein synthesis machinery is not impaired in GTG-induced obesity, which is therefore not associated with resistance to insulin for its effect on protein metabolism.
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PMID:Insulin and insulin-like growth factor I. Effects on protein synthesis in isolated muscles from lean and goldthioglucose-obese mice. 640 79

Type 2 diabetes is characterized by impaired insulin secretion. Some but not all studies suggest that a decrease in beta-cell mass contributes to this. We examined pancreatic tissue from 124 autopsies: 91 obese cases (BMI >27 kg/m(2); 41 with type 2 diabetes, 15 with impaired fasting glucose [IFG], and 35 nondiabetic subjects) and 33 lean cases (BMI <25 kg/m(2); 16 type 2 diabetic and 17 nondiabetic subjects). We measured relative beta-cell volume, frequency of beta-cell apoptosis and replication, and new islet formation from exocrine ducts (neogenesis). Relative beta-cell volume was increased in obese versus lean nondiabetic cases (P = 0.05) through the mechanism of increased neogenesis (P < 0.05). Obese humans with IFG and type 2 diabetes had a 40% (P < 0.05) and 63% (P < 0.01) deficit and lean cases of type 2 diabetes had a 41% deficit (P < 0.05) in relative beta-cell volume compared with nondiabetic obese and lean cases, respectively. The frequency of beta-cell replication was very low in all cases and no different among groups. Neogenesis, while increased with obesity, was comparable in obese type 2 diabetic, IFG, or nondiabetic subjects and in lean type 2 diabetic or nondiabetic subjects. However, the frequency of beta-cell apoptosis was increased 10-fold in lean and 3-fold in obese cases of type 2 diabetes compared with their respective nondiabetic control group (P < 0.05). We conclude that beta-cell mass is decreased in type 2 diabetes and that the mechanism underlying this is increased beta-cell apoptosis. Since the major defect leading to a decrease in beta-cell mass in type 2 diabetes is increased apoptosis, while new islet formation and beta-cell replication are normal, therapeutic approaches designed to arrest apoptosis could be a significant new development in the management of type 2 diabetes, because this approach might actually reverse the disease to a degree rather than just palliate glycemia.
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PMID:Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. 1250 99

Despite the high prevalence of diabetes mellitus, little is known about mortality associated with diabetes in Asia. Therefore, the authors followed 3,492 Chinese, Malay, and Asian Indian adults randomly selected from the general population in Singapore. Data on glucose tolerance, demographic characteristics, and other cardiovascular disease risk factors (lipid profile, blood pressure, smoking status, alcohol consumption, and obesity) were obtained in 1992. Vital status was determined as of December 31, 2001. There were 108 deaths over a period of 9 years. Impaired fasting glycemia or impaired glucose tolerance (IFG/IGT) (hazard ratio (HR)=1.39, 95% confidence interval (CI): 0.84, 2.31) and diabetes mellitus (HR=2.49, 95% CI: 1.58, 3.94) were associated with increased mortality after adjustment for age, gender, ethnic group, and educational level. Compared with Chinese with diabetes, Indians with diabetes experienced significantly greater mortality (HR=3.86, 95% CI: 1.76, 8.44) after adjustment for gender, age, educational level, smoking, hypertension, alcohol intake, and obesity. Undiagnosed diabetes and IFG/IGT were more common than known diabetes and also were associated with increased mortality. For reduction of mortality associated with IFG/IGT and diabetes, the authors recommend a screening program to detect undiagnosed diabetes and IFG/IGT along with aggressive treatment of diabetes after diagnosis.
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PMID:Associations of diabetes mellitus and ethnicity with mortality in a multiethnic Asian population: data from the 1992 Singapore National Health Survey. 1296 80

Metabolic syndrome is a cluster of cardiovascular risk factors. Pathogenesis of metabolic syndrome implies 3 potential etiological mechanisms: obesity and adipose tissue disorders, insulin resistance, and a constellation of independent factors. Clinical recognition of the metabolic syndrome is based on finding several well-recognized signs in clinical practice: abdominal obesity, elevated triglycerides, reduced HDL cholesterol, raised blood pressure, and elevated plasma glucose. In addition, other components commonly aggregate with the major components: elevated apolipoprotein B, small LDL particles, insulin resistance and hyperinsulinemia, impaired glucose tolerance (IGT), elevated C-reactive protein (CRP), and variation in coagulation factors (plasminogen activator inhibitor [PAI]-I and fibrinogen). Cardiovascular disease (CVD) is the primary clinical outcome of metabolic syndrome. Additionally, risk for type 2 diabetes is higher. Diabetes is itself a major risk factor for CVD. ATP III criteria for diagnosis of metabolic syndrome provide a practical tool to identify patients at increased risk for CVD. World Health Organization (WHO) and American Association of Clinical Endocrinologists (AACE) criteria require further oral glucose testing if IFG and diabetes are absent. IGT on OGTT denotes greater risk for diabetes than does metabolic syndrome without elevated fasting glucose.
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PMID:Metabolic syndrome--new insights into a growing entity. 1552 16

Low socioeconomic status (SES) is associated with type 2 diabetes. Inflammatory markers like C-reactive protein (CRP) are predictive of diabetes. It is unclear, whether inflammation may be a mechanism linking low SES to type 2 diabetes. In the population-based KORA Survey 2000, 766 men and 710 women aged 55 to 74 years were randomly selected in the Augsburg region (Southern Germany). An index for SES was defined using education, occupation, and income. In women but not in men, increased CRP concentrations were found with lower SES (p<0.01). This significant trend was no longer observed after adjusting for BMI and waist circumference (p=0.23). Low SES was significantly associated with the age-adjusted odds of having type 2 diabetes both in men (OR; 95%CI: 1.35; 1.14-1.60) and in women (2.01; 1.37-2.96). The risk of having diabetes associated with low SES was only slightly changed after adjusting for CRP, which was itself significantly related to diabetes. In multivariate analyses, adjusting for age, obesity, physical activity, smoking, alcohol intake, and CRP, low SES yielded only a borderline statistical significance in women (p=0.07), whereas no significant association with diabetes remained in men (p=0.14). After CRP was dropped from the full model, there was no change in the OR obtained for low SES (men: 1.30; 0.92-1.83; women: 1.54; 0.97-2.45). Low SES was not related to prediabetes (IFG, IGT), whereas CRP was significantly associated with diabetes precursors. In conclusion, inflammation appears not to play a major role linking low SES and type 2 diabetes in the elderly population.
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PMID:Is inflammation a causal chain between low socioeconomic status and type 2 diabetes? Results from the KORA Survey 2000. 1645 Feb 7

The authors conducted this study to evaluate the efficacy of a health check-up program and the health status of health care workers at Srinagarind Hospital, Faculty of Medicine, Khon Kaen University. The authors reviewed all yearly-check up charts of personnel who worked at Srinagarind Hospital from 2002 to 2003 including history taking, physical examination, and laboratory testings. There were 606 office workers and 1,024 nursing staff enrolled The mean ages of both groups were 38.9 and 36.5 years old, respectively. The office workers visited physicians significantly more often than the nursing staff (553 of 606 vs 271 of 1,024; p-value = 0.00). Obesity was found much more in office workers (127 of 472 versus 129 of 749). There were significant differences between the groups on impaired fasting plasma glucose, DM, HT, high cholesterol level, high triglyceride level, and significant elevation of ALT or AST (all p-value = 0.00). In the obese group, there was also a significantly higher number of cases who had high blood pressure, defined as IFG or DM, high cholesterol level, and high triglyceride level (p-value = 0.00) except the significant elevation of ALT or AST level. Cases of obesity with significant elevation of hepatic enzyme had many atherosclerotic risk factors. Therefore, metabolic derangements are the important problem for health care workers.
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PMID:Health status of health care workers at Srinagarind Hospital: experience from the Annual Health Check-up Program. 1647 Nov 10

Amrita Diabetes and Endocrine Population Survey (ADEPS) was conducted as a community-based cross-sectional survey to assess the prevalence of undetected diabetes mellitus (DM) and impaired glucose tolerance (IGT) and their possible relationship with various risk factors in an urban South Indian population. An initial house-to-house survey of adults between ages 18 and 80 years (n = 3069) was followed by a second phase consisting of health check-up and biochemical evaluations of participants (n = 986). DM and IGT were diagnosed as per WHO criteria. Reported prevalence of known diabetes mellitus in the survey was 9.0% (276/3069); (M-8.7% and F-9.2%). Among the screened subjects who underwent blood testing, the prevalence of newly diagnosed diabetes was 10.5%. The prevalence of IGT was 4.1% and IFG was 7.1%. Increasing age, obesity, positive family history of diabetes, abnormal subscapular triceps skin fold ratio and presence of acanthosis nigricans (AN) were all found to be associated with increased risk of DM. The finding of high prevalence of newly detected DM and IGT in this population of Kerala with the highest standards of health care and literacy level compared to other states of India, emphasizes the need for routine screening of high-risk groups for early detection of the disease. A simple cutaneous sign, acanthosis nigricans was independently associated with increased risk of type 2 diabetes in this survey and can be used as indication for screening for DM and IGT.
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PMID:Prevalence of known and undetected diabetes and associated risk factors in central Kerala--ADEPS. 1673 Aug 47

Prediabetes has been associated with an increased risk of cardiovascular disease and mortality. Soluble P-selectin (sP-selectin) is an index of platelet activation and also a risk factor for future vascular events. sP-selectin levels were investigated in prediabetic subjects who had no confounding factors such as hypertension, obesity or dyslipidaemia. sP-selectin, hsCRP levels and HOMA-IR indexes were measured in 40 prediabetic subjects (n = 24 for IFG and n = 16 for IGT) and age-, sex- and BMI-matched 40 healthy controls. sP-selectin levels in prediabetic subjects were not significantly different compared with those in controls (p = 0.12). Prediabetic group had similar hsCRP (p = 0.29), higher HOMA-IR indexes (p < 0.001) and lower HDL cholesterol levels (p = 0.001) when compared with healthy controls. The power of the study was 0.93 for sP-selectin, 0.7 for hsCRP and 1.0 for HOMA. Our data suggest that sP-selectin may not contribute to the prothrombotic state as well as the accelerated atherogenesis associated with prediabetes.
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PMID:The plasma levels of soluble P-selectin in subjects with prediabetes. 1693 45

Current reports estimate that type II diabetes (T2D) affects 5-8% of adults. Also recognized is a transitional group of patients whose fasting blood glucose is abnormal; yet, not considered high enough to be diagnosed as diabetes. Defined as "pre-diabetes" these individuals have impaired fasting glucose (IFG; fasting glucose 100-125 mg/dL), impaired glucose tolerance (IGT; 2 h glucose 140-199 mg/dL) or both. Two unifying features associated with IFG and IGT are their strong links to obesity and physical inactivity, which lead independently and collectively toward the erosion of various cellular processes affecting glucose control. In contrast, regular exercise positively influences IFG/IGT and obesity, thus representing an important therapy for preventing diabetes via the enhancement of several mechanisms of action. These include improved glucose metabolism, muscle respiratory capacity, mitochondrial respiratory chain activity and beta-oxidation. Contemporary exercise guidelines provided by various organizations recommend that exercise be performed at intensities ranging from 40% to 85% of maximal aerobic capacity. Unfortunately, little is known regarding the optimal intensity to best facilitate the physiological benefits associated with exercise. An evolving body of research shows that interval training produces greater changes in exercise capacity than traditional aerobic training. Interval training involves bouts of high exercise intensity (15s to 4 min; >90% VO(2max)) followed by a recovery period (40-50% VO(2max)) of equal or longer duration than the associated work interval. Though the net effect of interval training is aerobic, periodic excursions involving anaerobic energy pathways theoretically "push" the mitochondria to greater improvements in exercise capacity, mitochondrial biogenesis, enzymatic markers associated with glycolysis, aerobic metabolism and beta (beta)-oxidation. Though traditionally viewed as a training modality for athletes, a recent report has demonstrated that interval training is more effective than traditional aerobic exercise training in patients up to approximately 75 y of age and with low functional capacities (VO(2max) 13 ml/kg/min) by producing superior improvements in VO(2max), sub-maximal exercise tolerance, levels of peroxisome proliferator activator protein-gamma co-activator1alpha (PGC-1alpha), and quality of life indices more so than traditional aerobic exercise training. Erosion in these same markers is present in populations with pre-diabetes and T2D. The principal hypothesis of this paper is that interval training will provide a more powerful stimulus for improving insulin sensitivity than traditional low-to-moderate intensity aerobic conditioning. This theory further proposes that these affects will be due to greater changes in specific metabolic pathways associated with glycolysis, aerobic metabolism, beta-oxidation, and mitochondrial biogenesis.
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PMID:Exercise interval training: an improved stimulus for improving the physiology of pre-diabetes. 1870 13

OBJECTIVE Fibroblast growth factor (FGF)-21 is highly expressed in the liver and regulates hepatic glucose production and lipid metabolism in rodents. However, its role in the pathogenesis of type 2 diabetes in humans remains to be defined. The aim of this study was to quantitate circulating plasma FGF-21 levels and examine their relationship with insulin sensitivity in subjects with varying degrees of obesity and glucose tolerance. RESEARCH DESIGN AND METHODS Forty-one subjects (8 lean with normal glucose tolerance [NGT], 9 obese with NGT, 12 with impaired fasting glucose [IFG]/impaired glucose tolerance [IGT], and 12 type 2 diabetic subjects) received an oral glucose tolerance test (OGTT) and a hyperinsulinemic-euglycemic clamp (80 mU/m(2) per min) combined with 3-[(3)H] glucose infusion. RESULTS Subjects with type 2 diabetes, subjects with IGT, and obese subjects with NGT were insulin resistant compared with lean subjects with NGT. Plasma FGF-21 levels progressively increased from 3.9 +/- 0.3 ng/ml in lean subjects with NGT to 4.9 +/- 0.2 in obese subjects with NGT to 5.2 +/- 0.2 in subjects with IGT and to 5.3 +/- 0.2 in type 2 diabetic subjects. FGF-21 levels correlated inversely with whole-body (primarily reflects muscle) insulin sensitivity (r = -0.421, P = 0.007) and directly with the hepatic insulin resistance index (r = 0.344, P = 0.034). FGF-21 levels also correlated with measures of glycemia (fasting plasma glucose [r = 0.312, P = 0.05], 2-h plasma glucose [r = 0.414, P = 0.01], and A1C [r = 0.325, P = 0.04]). CONCLUSIONS Plasma FGF-21 levels are increased in insulin-resistant states and correlate with hepatic and whole-body (muscle) insulin resistance. FGF-21 may play a role in pathogenesis of hepatic and whole-body insulin resistance in type 2 diabetes.
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PMID:Circulating fibroblast growth factor-21 is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance. 1948 37


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