Non-diabetic Males Research Articles

Circulating Fatty Acids, Non-High Density Lipoprotein Cholesterol, and Insulin-Infused Fat Oxidation Acutely Influence Whole Body Insulin Sensitivity in Nondiabetic Men

Circulating lipids and tissue lipid depots predict insulin sensitivity. Associations between fat oxidation and insulin sensitivity are variable. We examined whether circulating lipids and fat oxidation independently influence insulin sensitivity. We also examined interrelationships among circulating lipids, fat oxidation, and tissue lipid depots. Fifty-nine nondiabetic males (age, 45.4 +/- 2 yr; body mass index, 29.1 +/- 0.5 kg/m(2)) had fasting circulating nonesterified fatty acids (NEFAs) and lipids measured, euglycemic-hyperinsulinemic clamp for whole body insulin sensitivity [glucose infusion rate (GIR)], substrate oxidation, body composition (determined by dual energy x-ray absorptiometry), and skeletal muscle triglyceride (SMT) measurements. GIR inversely correlated with fasting NEFAs (r = -0.47; P = 0.0002), insulin-infused NEFAs (n = 38; r = -0.62; P < 0.0001), low-density lipoprotein cholesterol (r = -0.50; P < 0.0001), non-high-density lipoprotein cholesterol (r = -0.52; P < 0.0001), basal fat oxidation (r = -0.32; P = 0.03), insulin-infused fat oxidation (r = -0.40; P = 0.02), SMT (r = -0.28; P < 0.05), and central fat (percentage; r = -0.59; P < 0.0001). NEFA levels correlated with central fat, but not with total body fat or SMT. Multiple regression analysis showed non-high-density lipoprotein cholesterol, fasting NEFAs, insulin-infused fat oxidation, and central fat to independently predict GIR, accounting for approximately 60% of the variance. Circulating fatty acids, although closely correlated with central fat, independently predict insulin sensitivity. Insulin-infused fat oxidation independently predicts insulin sensitivity across a wide range of adiposity. Therefore, lipolytic regulation as well as amount of central fat are important in modulating insulin sensitivity.

Nicotinic acid-induced insulin resistance is related to increased circulating fatty acids and fat oxidation but not muscle lipid content

Insulin resistance is associated with increased circulating lipids and skeletal muscle lipid content. Chronic nicotinic acid (NA) treatment reduces insulin sensitivity and provides a model of insulin resistance. We hypothesized that the reduction in insulin sensitivity occurs via elevation of circulating nonesterified fatty acids (NEFAs) and an increase in intramyocellular lipid (IMCL). A total of 15 nondiabetic males (mean age 27.4 ± 1.6 years) were treated with NA (500 mg daily for 1 week, 1 g daily for 1 week). Insulin sensitivity (glucose infusion rate [GIR]) was determined pre- and post-NA by euglycemic-hyperinsulinemic clamp. Substrate oxidation was determined by indirect calorimetry. Skeletal muscle lipid was assessed by estimation of long-chain acyl-CoA (LCACoA) and triglyceride (TG) content and by 1H-magnetic resonance spectroscopy quantification of IMCL (n = 11). NA reduced GIR (P = .03) and nonoxidative glucose disposal (P < .01) and increased fasting NEFAs (P = .01). The decrease in GIR related significantly to the increase in fasting NEFAs (r2 = .30, P = .03). The intrasubject increase in basal and clamp fat oxidation correlated with the decrease in GIR (r2 = .45, P < .01 and r2 = .63, P < .01). There were no significant changes in muscle LCACoA, TG, or IMCL content. Therefore, induction of insulin resistance by NA occurs with increased availability of circulating fatty acids to muscle rather than with increased muscle lipid content.

Influence of body composition on 5 year mortality in patients on regular haemodialysis.

Reduction of body mass index (BMI) significantly affects mortality in haemodialysis (HD) patients, but it remains to be determined which of the body components influences mortality. We examined the whole body composition of 262 HD patients by dual-energy X-ray absorptiometry (DEXA) (age: 60+/-12 years; HD duration 9+/-7 years; male/female: 177/85; diabetics, n=50) and subsequently followed mortality for 5 years. Patient age was significantly correlated with limb/trunk lean mass (LTLM) ratio (r=-0.350, P<0.01) and % fat content in whole tissue (r=0.145, P=0.02). There was a significant positive relationship between LTLM ratio and serum creatinine both in males (r=0.404, P<0.01) and females (r=0.267, P=0.01). Diabetic males and females both had a significantly lower LTLM ratio than non-diabetic males (P<0.01) and females (P<0.04). During the 5 years, 65 patients (24.8%) died mainly of cardiovascular diseases and infections. BMI was lower in the expired group than in survivors (P<0.04). LTLM ratio was significantly reduced in the expired group compared with the surviving males (0.629+/-0.097 vs 0.707+/-0.094; P<0.01) and females (0.611+/-0.101 vs 0.651+/-0.078; P<0.01). Cox's proportional hazards analysis revealed that the reduction of LTLM ratio was a significant determinant of death in men (P<0.01), while a lower percentage of fat content of trunk was a significant determinant of death in women (P<0.01). In contrast, BMI did not influence mortality in either sex. Measurements of regional lean and fat mass volumes by DEXA may be useful for predicting death in patients receiving long-term HD.

Multiple indexes of lipid availability are independently related to whole body insulin action in healthy humans.

An increase in muscle lipid content has been postulated to relate closely to the evolution of insulin resistance. We aimed to test whether the multiple indexes of lipid supply within man [namely, circulating triglycerides, skeletal muscle triglycerides (SMT), total and central fat mass, and circulating leptin] were independent predictors of insulin resistance, or whether triglycerides from different sources are additive in their influence on whole body insulin sensitivity. Whole body insulin sensitivity, body composition, and SMT content were determined in 49 sedentary, nondiabetic males (age, 20-74 yr; body mass index, 20-38 kg/m(2)). Insulin sensitivity was inversely associated with central abdominal fat (r(2) = 0.38; P < 0.0001), total body fat (r(2) = 0.21; P = 0.0003), SMT content (r(2) = 0.16; P = 0.005), and fasting triglycerides (r(2) = 0.24; P = 0.0003), nonesterified free fatty acid (r(2) = 0.19; P = 0.002), and leptin (r(2) = 0.35; P < 0.0001) levels. However, only central abdominal fat was significantly related to SMT content (r(2) = 0.10; P = 0.03). SMT content, circulating triglycerides, and measurements of total or central adiposity were independent predictors of whole body insulin sensitivity.

Sex steroid hormones, upper body obesity, and insulin resistance.

Low plasma levels of SHBG and free testosterone have been associated with increased insulin resistance and risk for type 2 diabetes in males. As truncal obesity, a condition accompanied by increased insulin resistance, is also associated with low SHBG and testosterone levels, the independent association of low free testosterone and SHBG with excessive insulin resistance remains to be determined. In this study we evaluated whether in normogonadic men, plasma levels of SHBG and free testosterone are primarily related to insulin resistance or to generalized and regional adiposity. Hyperinsulinemic-euglycemic clamps and iv glucose tolerance tests were performed in 24 healthy volunteer and 33 patients with mild type 2 diabetes. The 2 groups were chosen to have similar body mass index and were found to have similar body composition and fat distribution, assessed by underwater weighing, skinfold thickness, and magnetic resonance imaging of the abdomen. In the 2 groups combined, plasma levels of SHBG correlated inversely with fat accumulation in both sc and intraabdominal areas. Plasma levels of free testosterone correlated inversely with both truncal and peripheral skinfold thickness only in the nondiabetic men. No associations between plasma levels of sex steroid hormones and insulin resistance, hepatic glucose output, or insulin secretion were found to be independent of adiposity. Furthermore, although patients with diabetes were more insulin resistant than those without diabetes, the 2 groups had similar plasma concentrations of free testosterone (55 +/- 14 and 67 +/- 27 pmol/liter, respectively), SHBG (19 +/- 13 and 19 +/- 13 nmol/liter), estradiol (83 +/- 5 and 81 +/- 21 pmol/liter), and dehydroepiandrosterone sulfate (3.6 +/- 2.2 and 2.8 +/- 1.7 nmol/liter). We conclude that in normogonadal nondiabetic males, the variability in plasma bioavailable testosterone concentrations is predictive of the variability in fat deposition in the sc adipose tissue compartments of both truncal and peripheral areas. Low plasma levels of bioavailable testosterone do not independently predict excessive insulin resistance, beta-cell dysfunction, or hepatic glucose output in normogonadal men.

Exercise tolerance in type - 2 male diabetics

The objective of this study was to compare the exercisetolerance of a set of male diabetic Nigerians with non-diabetic male subjects. Ten male Type-2 diabetics between the ages of 35 and 50 years in good glycaemic control and ten male non-diabetic controls of similar age were exercised on the ergometer at uptake of 90% and 60% V02 max respectively for anaerobic and aerobic exercises. Cardiovascular and fatigue rates or times to fatigue were then determined in both groups.In both diabetics and controls, the time to fatigue was significantly longer during exercise at 60% VO2max than at 90% VO2max (P&lt;0.01). During aerobic exercise, the mean times to fatigue were very similar in the diabetic and control men {427.5 (38.0) secs. V 439 .0 (56.9) secs. p&gt; 0.1}. The diabetic men fatigued more easily than controls under anaerobic condition (p 0.1 &gt; p &gt; 0.05). Type 2 male diabetics with good glycaemic control appear to tolerate aerobic exercise as well as non-diabetic males, but less so during anaerobic exercise. This difference in aerobic and anaerobic exercise tolerance should be borne in mind in prescribing exercise regimes in patients with type 2 diabetes mellitus.

Influence of gender on dilatation of the basilar artery during diabetes mellitus

The first goal of the present study was to examine the influence of gender on reactivity of the basilar artery. The second goal of this study was to examine the effect of diabetes mellitus on reactivity of the basilar artery in male and female rats. We examined in vivo responses of the basilar artery in male and female nondiabetic and diabetic rats in response to a nitric oxide synthase (NOS)-dependent (acetylcholine) and -independent (nitroglycerin) agonist. In nondiabetic male and female rats, acetylcholine and nitroglycerin produced dose-related dilatation of the basilar artery. However, the magnitude of vasodilatation in response to acetylcholine and a high concentration of nitroglycerin was significantly greater in female than in male rats. Acetylcholine (1.0 μM) dilated the basilar artery by 11±2% in nondiabetic males versus 25±4% in nondiabetic females ( P<0.05). Nitroglycerin (1.0 μM) dilated the basilar artery by 37±8% in nondiabetic males versus 62±5% in nondiabetic females ( P<0.05). Thus, there is a significant effect of gender on reactivity of the basilar artery during physiologic conditions. Dilatation of the basilar artery in response to acetylcholine, but not nitroglycerin, was impaired in diabetic male and female rats compared to their nondiabetic counterparts. Acetylcholine (1.0 μM) dilated the basilar artery by only 5±1% in diabetic males and by only 4±1% in diabetic females. In summary, dilatation of the basilar artery in response to NOS-dependent agonist was significantly greater in nondiabetic female than in nondiabetic male rats. In addition, diabetes mellitus impaired NOS-dependent dilatation of the basilar artery not only in male rats, but also in female rats. We suggest that the results of these studies provide insight into the pathogenesis of cerebrovascular abnormalities observed in postmenopausal women.

Association of Hypertension and Non-Insulin-Dependent Diabetes Mellitus in the Saudi Population

Saudi Arabia has a high prevalence of diabetes mellitus (DM). Several studies have shown that hypertension (HT) occurs frequently in obese individuals. This study was conducted to determine the prevalence of HT in Saudi diabetic patients. A total of 13,519 nondiabetic and 1286 diabetic adult subjects diagnosed during the National Program for the Study of DM, in which household screening was carried out, were included in the study. The diagnosis of DM and HT was based on the criteria of the World Health Organization. From the total group, the prevalence of HT in nondiabetic males and females was 4.48% and 2.8%, respectively, while it was 11.44% and 15.98% in the diabetic males and females, respectively. The subjects were classified according to the province to which they belonged, and the prevalence of HT was calculated in the diabetic and nondiabetic group. In the Central, Eastern and Western Provinces, female diabetics had a significantly higher HT prevalence compared to male diabetics, however, in the Southern and Northern Provinces, the prevalence rate was almost the same. In all provinces the increase in prevalence of HT in diabetics was significantly higher in the females compared to the males. Since HT prevalence increases significantly in diabetics, and this association leads to several cardiovascular complications, it is necessary to adopt measures for the control of DM and HT in the Saudi population.

Prevalence of overwieght and obesity in diabetic and non-diabetic Saudis

A total of 14 660 individuals were included in the study. A fasting blood sample and 2-hour post-glucose load blood sample from each participant were analysed for blood sugar. Participants were classified as diabetic or non-diabetic and as either obese [BMI &gt; 30 kg/m2], overweight [BMI 25-29.9 kg/m2] or normal [BMI &lt; 25 kg/m2]. The prevalence of obesity was calculated in the total sample and separately for diabetic and non-diabetic males and females. The results showed obesity and overweight in 13.05% and 27.23% of males and 20.26% and 25.20% of females respectively. The prevalence of both obesity and overweight were significantly higher among diabetics than non-diabetics. In each province, diabetics had a significantly higher prevalence of obesity than non-diabetics. Several interprovincial variations were seen. Public education on obesity and overweight and ways to decrease them are recommended in Saudi Arabia

Endurance training increases the beta-adrenergic lipolytic response in subcutaneous adipose tissue in obese subjects.

The aim of this study was to assess, by longitudinal follow-up, the influence of aerobic training on the in vivo lipolytic activity of adipose tissue in obese male subjects. Eleven obese non-diabetic males, aged 41.5+/-5.77 (range 27-49 y) with body mass index (BMI) 36.5+/-4.5 kg/m2 (range 29.4-47.1 kg/m2) participated in the study. Subjects took part in a 12-week aerobic training program. Before and after training, microdialysis of abdominal subcutaneous adipose tissue (SCAT) was carried out, using perfusion with graded doses of the beta-adrenergic agonist isoprenaline and a single dose of the phosphodiesterase inhibitor theophylline. In addition, the response of plasma glycerol and free fatty acids (FFAs) to intravenous infusion of graded doses of isoprenaline was tested. The training did not induce significant weight loss and promoted an increase in maximum aerobic capacity (P<0.05). The increase of extracellular glycerol in SCAT in response to isoprenaline perfusion was enhanced after the training (P<0.05), while no change in the response of interstitial glycerol to theophylline action was observed. The training did not elicit a change in the isoprenaline-induced changes of blood flow in adipose tissue. The increases of plasma FFAs and glycerol in response to intravenous isoprenaline infusion, were significantly enhanced after training. The present study shows that aerobic training induced an increase in the response of plasma and subcutaneous adipose tissue concentration of glycerol to beta-adrenergic stimulation. The effect of an agent acting at the post-receptor level (theophylline) in SCAT was not modified by training.

ACTH and cortisol response to combined corticotropin releasing hormone-arginine vasopressin stimulation in obese males and its relationship to body weight, fat distribution and parameters of the metabolic syndrome.

To investigate the activity of the hypothalamic-pituitary-adrenal (HPA) axis in male obesity and its relationship with several prominent parameters of the metabolic syndrome. A cross-sectional clinical study of the activity of the HPA axis in groups of obese males and normal-weight controls. Seventeen obese non-diabetic males with a body mass index (BMI) >28 and eight normal-weight controls were examined. Fat free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance, and the waist-to-hip circumference ratio (WHR) was calculated in all subjects. Baseline samples were taken for sex hormone and lipid determination, and an oral glucose tolerance test (OGTT) was performed for glucose and insulin determination. The activity of the HPA axis was determined by the combined administration of human corticotropin releasing hormone (CRH) (100 microg) and arginine vasopressin (AVP) (0.3 IU). As expected, FFM and FM and the WHR were higher in obese men than in controls, as were fasting insulin and stimulated (as area under the curve (AUC)) glucose and insulin concentrations. Baseline adrenocorticotropin (ACTH) and cortisol concentrations were similar in both groups, but stimulated (as AUC), ACTH was higher (P < 0.05) in obese subjects than in controls, whereas no significant difference in cortisolAUC was present. Since the main differences between obese subjects and controls were present during the early 30 min of the test, the correlation coefficients between total and incremental ACTH(AUC 0-30 min) and CortisolAUC 0-30 min and all other variables were analyzed. A significant correlation coefficient was present between them and all anthropometric parameters, fasting insulin and insulinAUC, but not with androgens and gonadotrophins. In addition, a significant correlation was present between total and incremental ACTH(AUC 0-30 min) and triglyceride concentrations. However, after adjusting for BMI or FM values, all correlation coefficients became non-significant, except the one between incremental ACTH(AUC 0-30 min) and insulinAUC (P < 0.05). These findings indicate that obese men may also have an altered pituitary response to combined CRH/AVP stimulation, which appears to be predominantly related to body size and total body fat. ACTH hyperresponsiveness after CRH/AVP stimulation also appears to be related to hyperinsulinaemia, but underlying mechanisms of this relationship remain to be elucidated.

Impaired ventilatory function and elevated insulin levels in nondiabetic males: the Normative Aging Study.

Lower levels of baseline ventilatory function have consistently been associated with increased risk of cardiovascular mortality in prospective studies, but the underlying mechanisms are not known. Increased risk of coronary heart disease is associated with higher serum insulin levels. This report examines the relationship between ventilatory function and indirect measures of insulin resistance. Cross-sectional data from 922 nondiabetic participants in the Normative Aging Study were analysed using multiple linear regression models with adjustment for potential confounders. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were examined in relation to indicators of insulin resistance, i.e. fasting insulin and the fasting insulin resistance index (FIRI). Diabetics were excluded because impaired insulin secretion interferes with the validity of these as measures of insulin resistance. Fasting insulin and FIRI were negatively correlated with FVC and FEV1 (all p< 0.001). These associations persisted after adjusting for potential confounders including age, height, body mass index, waist to hip circumference ratio, physical activity, alcohol intake and smoking in separate multiple linear regression models, for both insulin (all p< or =0.0008) and FIRI (all p< or =0.0001). Negative cross-sectional associations between ventilatory function and indirect measures of insulin resistance were found in nondiabetic males. Insulin resistance may contribute to the previously unexplained association between ventilatory function impairment and cardiovascular mortality. Mechanisms underlying the relationship between insulin resistance and decreased ventilatory function remain to be elucidated.

Low educational status is a risk factor for mortality among diabetic people.

Diabetes mellitus and its complications are an important cause of mortality in Western populations. The purpose of the present study was to examine the relationship between self-reported diabetes mellitus, gender, attained level of education, and socio-economic resources to all-cause mortality risk in a simple random sample of 39055 subjects, aged 25 to 74 years. Follow-up data were obtained for a maximum of 16 years, from baseline (1979-1985) to 31 December 1995. Diabetic males (2.2% of the male study group) had a relative risk (RR) for total mortality of 2.24 (CI = 1.96-2.57), adjusted for age, education, marital status, housing tenure, and car ownership, compared with non-diabetic males. The corresponding figure for females with diabetes (1.9%) was RR = 3.67 (CI = 3.16-4.27). Diabetic women had the highest age-adjusted mortality risk for coronary heart disease (CHD) of 8 compared with non-diabetic women. The corresponding RR for men was just below 3 (p<0.0001). Males and females (with and without diabetes) of low attained educational level had a RR = 1.26 (CI = 1.15-1.39) and RR = 1.54 (CI = 1.31-1.81), respectively. When analysing all people with diabetes separately, adjusting for sex and age, low-educated subjects had a 40% excess all-cause mortality compared with high-educated subjects. We conclude that diabetic women have a very high relative risk for CHD mortality compared to non-diabetic women. Furthermore, diabetic people with a low attained level of education, have an increased vulnerability to, and a higher total mortality.

The relationship between the glycaemic response to breakfast cereals and subjective appetite and food intake

To determine the relationship between the glycaemic response to food and satiety, the effects of three treatments (shredded wheat (SW) + glucose (glu), SW + fructose (fru), and water) on blood glucose and food intake, measured over two separate time periods (30 and 120 minutes), were studied in 13 normal weight, non-diabetic males. Blood glucose concentrations were affected by treatment (SW+glu > SW+fru > water; p<0.05) at t = 15 and 30 during the 30 min sessions, and at t = 15, 30, 45, and 60 during the 120 min sessions. At t = 90 and 120, SW+glu > water = SW+fru. Energy intakes 30 min and 120 min after treatment were lower after both SW treatments than when water alone was consumed (p<0.05), but there was no difference between the SW treatments. Total energy intake (preload + meal) did not differ between treatments in the 30 min session, however in the 120 min session the SW+glu treatment resulted in total energy intake greater than water alone. No relationship was found between the effects of treatment on glycaemic response and satiety.

Clinical features in persons with a family history of diabetes compared to controls (The Second Generation Fredericia Study).

To compare clinical and biochemical features in non-diabetic persons with a family history of non-insulin dependent diabetes mellitus (NIDDM) to non-diabetic persons without a family history of diabetes. Cross-sectional study. Population-based survey in Fredericia, Denmark. Seven hundred and forty subjects, the second generation of an earlier defined cohort was examined. The median age was 48 (range 26-65) years. Of the 740 subjects 696 were non-diabetic. The subjects had a clinical examination. Known risk factors for development of diabetes and cardiovascular disease. More offspring of diabetic persons had NIDDM (chi 2 = 6.36, P < 0.05). Non-diabetic males with a family history of diabetes had a higher BMI fasting blood glucose, and triglycerides compared to males without a family history of diabetes. Non-diabetic females with a family history of diabetes had a higher BMI, fasting blood glucose. HbA1C, diastolic blood pressure, and lower HDL-cholesterol than female offspring of non-diabetics. In a multiple regression model we found that non-diabetic off-spring of diabetic persons had higher fasting blood glucose and HbA1C compared to offspring of non-diabetic persons when adjusted for the independent variables age, BMI, WHR, and sex. Our results may indicate that the only inherited factors from NIDDM patients are plasma blood glucose. HbA1C and increased BMI which may be an indication for later diabetes, whereas other cardiovascular risk factors may be inherited independently of diabetes but associated with BMI.

Delayed onset of insulin activation of the insulin receptor kinase in vivo in human skeletal muscle.

During the infusion of insulin in vivo, the rate of activation of glucose disposal lags significantly behind the rate of increase in serum insulin levels. To determine whether this delay was related to transcapillary transport of insulin, we determined increments in serum insulin levels, glucose disposal rates (GDR), and insulin receptor (IR) kinase activity measured during continuous infusions of insulin (40 and 120 mU.m-2.min-1) administered to 8 nondiabetic males; similar studies were done at 1,200.m-2.min-1 in 2 of the subjects. Half-maximal insulin levels were achieved at a mean of 4.9 and 7.2 min during the 40 and 120 mU.m-2.min-1 clamps, respectively, with corresponding half-maximal GDR stimulation at a mean of 59 and 47 min. Unlike the rise in insulin levels, IR kinase activation was much slower with half-maximal activity occurring at approximately 40-60 min in the 2 clamps. Thus, the rise in serum insulin levels in each clamp was much faster than the increment in either kinase activity or glucose disposal. Insulin infusion increased both IR kinase and GDR maximally approximately 10-fold, with half-maximal stimulation at approximately 3,600 and approximately 700 pM, indicating spare kinase for glucose disposal. These results demonstrate that the delay in stimulation of glucose disposal by insulin is related to a rate-limiting step between the intravascular space and the cell-surface of skeletal muscle. This may involve delayed transendothelial transport of insulin.

Functional changes in salivary glands of autoimmune disease-prone NOD mice.

Lymphocytic infiltration of the salivary glands in autoimmune diseases results in the human condition known as xerostomia. To date, an animal model for the autoimmune development of salivary gland dysfunction has yet to be described. With the autoimmune diabetes-prone nonobese diabetic (NOD) mouse strain, salivary flow rates and total saliva protein concentration in both male and female mice showed a progressive decline in the nondiabetic and diabetic states. Submandibular gland weight decreased from control mice with the progression to onset of diabetes in both sexes, whereas the weight of the parotid gland remained unchanged. The level of saliva amylase activity, when measured relative to unit volume, decreased in nondiabetic males but increased upon onset of diabetes to control values. When expressed relative to protein concentration in saliva, amylase activity was depressed for both sets of NOD mice but was higher upon diabetes onset than in the nondiabetic animals. In females a similar pattern was observed except that amylase activity expressed relative to unit volume was not significantly depressed in either set of NOD mice. The same observations were made for glandular amylase activity. The level of epidermal growth factor (a product of the ductal cells of the submandibular gland) was reduced over 500- and 18-fold for male and female diabetic mice, respectively. Sodium dodecyl sulfate polyacrylamide gels of total saliva showed changes in mobility as well as concentration of several proteins in the NOD mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of body mass index and fat distribution on insulin sensitivity, secretion, and clearance in nonobese healthy men.

The effects of variation in body mass index (BMI; kg/m2) and body fat topography on insulin sensitivity, secretion, and clearance were determined in a group of 146 nonobese nondiabetic males. Volunteers underwent an i.v. glucose tolerance test, with determination of plasma glucose, insulin, and C-peptide levels. BMI was taken as a measure of overall adiposity, while skinfold thickness ratios were used to assess the centrality of fat distribution and the localization of central fat within the trunk. Measurements of insulin sensitivity, secretion, and clearance were obtained by mathematical modelling of the i.v. glucose tolerance test concentration profiles. Increasing BMI and centrality of fat distribution had no significant effect on glucose tolerance, but were independently associated with diminished insulin sensitivity and increased insulin secretion. The elevation in secretion occurred almost entirely during the second phase of pancreatic insulin release. These results show that the variations in insulin sensitivity and secretion that have often been reported in obesity are also present in a group within the normal range of BMI. However, the absence of any decrease in hepatic uptake, also reported in the obese, indicates that this might be an additional mechanism recruited to maintain glycemic control at higher levels of adiposity. Localization of central fat in the lower trunk was correlated with elevated first phase insulin secretion, but no concomitant change in insulin sensitivity. There may, therefore, be a direct effect of the distribution of central fat on insulin secretion.

Limited Joint Mobility, Dupuytren's Contracture and Retinopathy in Type 1 Diabetes: Association with Cigarette Smoking

To examine the associations between cigarette smoking, connective tissue changes, and diabetic retinopathy, a detailed smoking history was elicited from 150 normotensive non-diabetic subjects, and from 266 randomly selected adult patients with Type 1 diabetes, after examination for limited joint mobility, Dupuytren's contracture, and diabetic retinopathy. Mean insulin dose and current glycosylated haemoglobin concentrations were comparable in diabetic smokers and non-smokers. The historical duration of smoking correlated with the duration of diabetes (r = 0.72, p less than 0.001). In diabetic patients limited joint mobility was positively associated with retinopathy, being found in 73/147 (50%) patients with retinopathy compared with 20/114 (18%) without retinopathy (chi 2 = 28.9, p less than 0.001), and also with Dupuytren's contracture, 19/34 (56%) of patients with limited joint mobility having Dupuytren's contracture, compared with 76/232 (33%) of patients without Dupuytren's contracture (chi 2 = 7.05, p less than 0.01). Limited joint mobility was observed in 50% of diabetic smokers compared with 25% of non-smokers (odds ratio = 2.87 (corrected for diabetes duration), 95% confidence interval 1.64-5.01). Diabetic retinopathy was weakly associated with smoking (odds ratio 1.09; 95% confidence interval 0.60-1.96). There was however an increased prevalence of background retinopathy among male smokers (50% vs 29%; chi 2 = 6.88, p less than 0.01). In non-diabetic males limited joint mobility was observed in 37% of smokers but only in 11% of non-smokers (NS), while 33% of smokers and 8% of non-smokers had Dupuytren's contracture (p = 0.012). These results suggest that cigarette smoking contributes to the development of extra-articular connective tissue changes in both diabetic patients and non-diabetic subjects, and possibly to the development of diabetic retinopathy.

Low serum apolipoprotein A-I in acute myocardial infarction survivors with normal HDL cholesterol

High density lipoprotein (HDL) cholesterol, apolipoprotein A-1 (apo A-I), γ-glutamyl-transferase, testosterone and oestradiol were determined in plasma in non-diabetic males who had survived an acute myocardial infarction (AMI) before the age of 60. They also had serum levels of cholesterol below 7.0 mmol/l 1 year after the AML On the basis of diastolic blood pressure they were subdivided into 2 groups with diastolic blood pressures below 90 mm Hg (n = 39), and with or above 95 mm Hg (n = 21) and then compared with an age-matched male non-diabetic reference group (n = 32). There were no significant differences in the levels of HDL cholesterol, γ-glutamyl-transferase, and sex hormones between the AMI groups and the reference group. Reduced plasma levels of apo A-1 were found in the AMI groups.