Effect of cigarette smoking on insulin resistance risk

ObjectivesSmoking is one of the main risk factors for cardiovascular disease (CVD). The mechanism(s) of the effects of smoking on CVD are not clearly understood; however, a number of atherogenic characteristics, such as insulin resistance have been reported. We aim to investigate the effects of cigarette smoking on insulin resistance and to determine the correlation between this parameter with smoking status characteristics.Study designThis study was conducted on 138 non-smokers and 162 smokers aged respectively 35.6 ± 16.0 and 38.5 ± 21.9 years. All subjects are not diabetic.MethodsFasting glucose was determined by enzymatic methods and insulin by chemiluminescence method. Insulin resistance (IR) was estimated using the Homeostasis Model of Assessment equation: HOMA-IR = [fasting insulin (mU/L) × fasting glucose (mmol/L)]/22.5. IR was defined as the upper quartile of HOMA-IR. Values above 2.5 were taken as abnormal and reflect insulin resistance.ResultsCompared to non-smokers, smokers had significantly higher levels of fasting glucose, fasting insulin and HOMA-IR index. These associations remained significant after adjustment for confounding factors (age, gender, BMI and alcohol consumption). A statistically significant association was noted between the smoking status parameters, including both the number of cigarettes smoked/day and the duration of smoking, and fasting insulin levels as well for HOMA-IR index. Among smokers, we noted a positive correlation between HOMA-IR index and both plasma thiocyanates and urinary cotinine.ConclusionOur results show that smokers have a high risk to developing an insulin resistance and hyperinsulinemia, compared with a matched group of non-smokers, and may help to explain the high risk of cardiovascular diseases in smokers.     

High plasma HDL-C attenuates stress hyperglycemia during acute phase of myocardial infarction

ObjectiveDuring myocardial infarction (MI), a transient decrease of both insulin sensitivity and secretion triggers stress hyperglycemia, which is followed by a substantial increase in mortality. Recent findings in cellular models indicate that HDL may act on glucose homeostasis by improving insulin sensitivity and secretion. In this study, we explored this potential effect in patients during the acute phase of MI.MethodsPlasma glucose, insulin and C-peptide were measured at admission in the first 24 h and on the fifth day after MI with ST-segment elevation in 183 consecutive non-diabetic patients. Patients were divided into HDL-C quartiles for the analyses (Q1: <31, Q2: 31–38, Q3: 38–47 and Q4: >47 mg/dL). The Homeostasis Model Assessment version 2 was used to assess insulin sensitivity (HOMA2S) and beta-cell function (HOMA2B).ResultsOn admission, no difference was found between the quartiles in glucose (p = 0.6), insulin (p = 0.6) or C-peptide (p = 0.5) levels, HOMA2S (p = 0.9) or HOMA2B (p = 1.0). On the fifth day there was a reduction in glucose levels whose intensity was directly proportional to the HDL-C quartile (p < 0.001). At the same time, there was a reduction in plasma insulin (p < 0.001) and C-peptides (p < 0.001) whose magnitude was inversely proportional to the HDL-C quartile. Consistently, the increase of HOMA2S (p < 0.001) and HOMA2B (p = 0.01) were also positively associated with HDL-C levels. Furthermore, plasma HDL-C levels were inversely and independently associated with blood glucose change during the acute phase.ConclusionThis study demonstrates the association between low plasma HDL-C levels and increased duration of stress hyperglycemia during MI and suggests in humans the interaction between HDL and insulin secretion and sensitivity.     

Glucagon-stimulated insulin secretion in patients with type 2 diabetes mellitus: support for the concept of glucose toxicity.

Parameters of blood glucose control and insulin secretion were evaluated in 114 patients with type 2 diabetes mellitus, who were no longer controlled satisfactorily by maximal doses of oral hypoglycaemic agents, and compared with those obtained in 11 healthy control subjects, 32 patients with recently-diagnosed type 2 diabetes, and 16 tablet-treated and 36 insulin-treated patients. Newly-diagnosed patients were slightly younger (60 +/- 13 yr) and had a slightly higher body mass index (29.4 +/- 6.5 kg/m2). Known duration of diabetes was 9 yr (range 1-37) in secondary failure, and 11 yr (range 1-31) in insulin-treated patients. Fasting blood glucose was the highest (13.8 +/- 2.8 mmol/l) in secondary failure and newly-diagnosed patients (12.6 +/- 3.8 mmol/l) compared to tablet-treated (8.7 +/- 3.3 mmol/l) and insulin-treated patients (9.6 +/- 3.2 mmol/l, p less than 0.05). HbA1c levels were comparably elevated. In insulin-treated patients, fasting plasma C-peptide levels were lower relative to the mutually comparable levels in the other 3 diabetic groups. Fasting plasma insulin levels did not differ between the 4 diabetic groups. C-peptide release after glucagon (C-peptide AUC) was comparable in all 4 diabetic groups, although in tablet-treated patients the ratio C-peptide AUC/fasting blood glucose was higher (p less than 0.05). We conclude that the clinical usefulness of determining residual insulin secretion in type 2 diabetic patients is limited, and that the similar reduction of insulin secretion in severely hyperglycaemic newly-diagnosed and secondary failure type 2 diabetic patients supports the concept of "glucose toxicity".     

Effects of short-term low- and high-carbohydrate diets on postprandial metabolism in non-diabetic and diabetic subjects

Background and aimLow-fat high-carbohydrate diets raise plasma triacylglycerol (TG) concentrations. To test whether the nature of the carbohydrate affects metabolic responses, we conducted a randomized cross-over study using a short-term, intensive dietary modification.Methods and resultsEight non-diabetic subjects and four subjects with diet-controlled type 2 diabetes participated. They followed three isoenergetic diets, each for 3 days: high-fat (50% energy from fat), high-starch and high-sugar (each 70% energy from carbohydrate). Normal foods were provided. We measured plasma TG and glucose concentrations, fasting and after a standard test meal, on day 4 following each dietary period. Fasting TG concentrations were greatest following the high-sugar diet (mean ± SEM for all subjects 1900 ± 420 μmol/l) and lowest following high-fat (1010 ± 130 μmol/l) (P = 0.001); high-starch (mean 1500 ± 310) and high-fat did not differ significantly (P = 0.06). There was a greater effect in the diabetic subjects (diet × diabetes status interaction, P = 0.008). Postprandial TG concentrations were similarly affected by prior diet (P < 0.001) with each diet different from the others (P ≤ 0.01). The elevation of fasting TG on the high-sugar versus high-fat diet was strongly related to the average fasting TG concentration (P = 0.01 across both diabetic and non-diabetic subjects). Fasting glucose concentrations were not affected by prior diet but postprandial glucose concentrations were (P = 0.018), with significantly higher values after the high-fat than the high-sugar diet (P = 0.03).ConclusionsThe short-term TG-raising effect of a very low-fat diet is dependent upon the nature of the carbohydrate, with a greater effect of a sugar-rich than a complex-carbohydrate-rich diet.     

Early decrease in resting energy expenditure with bedtime insulin therapy

AimsIn type 2 diabetes (T2D), insulin-induced weight gain may stem from a reduction in resting energy expenditure (REE). We sought to determine the early effects of insulin introduction on REE in 20 poorly controlled T2D patients.MethodsAfter improving the glycaemia, REE was measured on Day 0 and Day 4 during two treatment regimens: bedtime insulin (n = 10, group 1); and one off (3-day) intravenous insulin infusion (n = 10, group 2).ResultsBoth groups were similar in age, gender, BMI, C-peptide, HbA_1c and initial REE. By Day 4, fasting glycaemia had similarly improved in both groups: group 1: −5.3 ± 2.7 mmol/L vs group 2: −5.8 ± 4.2 mmol/L. In group 2, the second REE was measured 12 h after stopping the intravenous insulin infusion, whereas subcutaneous insulin was maintained in group 1. REE did not change in group 2 (−1.3 ± 6.5%), whereas it decreased significantly in group 1 (−8.0 ± 7.0%; P < 0.05).ConclusionBedtime insulin led to an early and specific reduction in REE.     

Insulin requirement in non-insulin-dependent diabetes mellitus: relation to simple tests of islet B-cell function and insulin sensitivity

Evaluation of simple tests of islet B-cell function and insulin sensitivity as predictors of metabolic control was performed during 3 months of insulin withdrawal in 25 insulin-treated diabetic subjects. All patients had a glucagon stimulated plasma C-peptide concentration above 0.33 nmol/l and a fasting plasma C-peptide concentration above 0.20 nmol/l a few days before insulin withdrawal. Insulin sensitivity was measured as the glucose disappearance rate (k) during an intravenous insulin tolerance test. Two patients were considered insulin-requiring due to high fasting blood glucose levels (greater than 20 mmol/l) and two patients due to an increase in glycosylated haemoglobin of more than 1.1% (greater than approximately 3SD) in combination with weight loss. None of the remaining patients had a significant increase in glycosylated haemoglobin. An inverse correlation was found between stimulated C-peptide levels and insulin sensitivity (r = 0.41, p less than 0.05). Fasting and stimulated C-peptide concentrations of 0.40 and 0.70 nmol/l, respectively, separated non-insulin-requiring patients from a group consisting of both insulin- and non-insulin-requiring patients. At these C-peptide levels the predictive value of a positive test was 100% while the predictive value of a negative test was as low as 33% or 27% depending on whether fasting or stimulated C-peptide concentration was used. Including the k value in the prediction only increased the predictive values of negative tests to 40% and 33%, respectively.     

Hyperinsulinemia and insulin resistance are independently associated with plasma lipids, uric acid and blood pressure in non-diabetic subjects. The GISIR database

Background and aimsWe evaluated whether hyperinsulinemia and/or insulin resistance are independently associated with plasma lipids, uric acid and blood pressure in non-diabetic subjects.Methods and resultsA database of non-diabetic Italian subjects has recently been set up using data from hyperinsulinemic euglycemic clamp studies carried out using the standard technique (40 mU per min per square meter of body surface area). In this database we evaluated the relationships between fasting plasma insulin (FPI), glucose metabolized during clamp (M) and plasma levels of triglycerides (TG), high density lipoprotein cholesterol (HDL-C), uric acid (UA) as well as blood pressure (BP) in non-diabetic subjects with fasting plasma glucose <6.1 mmol/l. Parallel analyses were conducted in all subjects in the database (n = 1093) and in those with all variables available (n = 309).In the univariate analysis both FPI and M were significantly correlated with TG, HDL-C, UA and BP (systolic, diastolic and mean). Multivariate regression analyses including center, sex, age, body mass index (BMI), FPI and M as independent variables showed that: (1) TG and UA were positively correlated with FPI and negatively correlated with M; (2) HDL-C was negatively correlated with FPI and positively correlated with M; and (3) BP was negatively correlated with both FPI and M. Analyses of covariance showed that, after adjusting for center, sex, age and BMI, subjects with isolated hyperinsulinemia or isolated insulin resistance had higher TG and UA and lower HDL-C. Subjects with isolated insulin resistance had also higher BP whereas subjects with isolated hyperinsulinemia had lower BP. Subjects with both defects had a worse profile.ConclusionsHyperinsulinemia and insulin resistance might contribute with distinct and independent mechanisms to the development of several metabolic and hemodynamic disorders often clustering in the same individual. In particular, hypertriglyceridemia, low HDL-cholesterol and hyperuricemia seem to be related to both hyperinsulinemia and insulin resistance, whereas hypertension seems to be related only to insulin resistance.     

Effects on post-prandial glucose and AGE precursors from two initial insulin strategies in patients with Type 2 diabetes uncontrolled by oral agents

ObjectiveProgressive β-cell dysfunction in Type 2 diabetes results in the need for insulin therapy in many patients. Yet the best regimen to prescribe to patients transitioning from oral anti-hyperglycemic drugs (OADs) is not clear. We sought to compare the effects of two standard initial insulin strategies (basal insulin alone versus premixed insulin) on post-prandial glucose metabolism and precursors of advanced glycation end-products in patients with type 2 diabetes suboptimally controlled on OADs.Research Design and MethodsThis was a 6-month, open-label, single-center study using a cross-over design. 14 subjects were randomized to one of two protocols: once daily insulin glargine or twice-daily 75%/25% neutral protamine lispro/lispro mix. At 12 weeks, the subjects were crossed-over to the opposite protocol. During each period, insulin doses were titrated to target fasting blood glucose of 90–110mg/dL. At baseline and after the two 12-week treatment periods, subjects were studied in the Clinical Research Center; they consumed three liquid mixed isocaloric meals at 4-h intervals, and glucose, free fatty acids (FFA), lipids, and α-dicarbonyls (3-deoxyglucosone [3-DG] and methylglyoxal [MG]) were measured before and after each meal. Patient data were analyzed in the context of their assigned insulin strategy groups.ResultBoth insulin regimens led to a significant improvement in glycemic profiles, including fasting glucose and HbA1c, compared to baseline. However, mean post-prandial glucose was lower with lispro mix than with glargine (153 ± 36 vs. 199 ± 49 mg/dL, respectively; P = 0.001). Likewise, there was a reduction in both fasting (48 ± 13 vs. 57 ± 19, P = 0.047) and post-prandial (53 ± 19 vs. 63 ± 23; P = 0.007) 3DG levels with lispro mix as compared to glargine. No differences were noted in MG concentrations.ConclusionIn type 2 diabetes patients failing OAD therapy, an initial insulin regimen of twice daily premixed insulin results in significantly improved post-prandial glucose levels as well as a reduction in a precursor of AGEs. The effect of these two initial insulin regimens on long-term diabetic complications requires further study.     

Erythrocyte mechanical fragility is increased in patients with type 2 diabetes

BackgroundAnemia is common among patients with type 2 diabetes. We determined whether type 2 diabetic patients significantly differed in erythrocyte mechanical fragility as compared with nondiabetic subjects.MethodsWe recruited 25 Caucasian patients with type 2 diabetes (14 men and 11 women; mean age 58 ± 8 years) and 25 age-, race- and sex-matched nondiabetic individuals. The fragility of erythrocytes was tested by inducing mechanical hemolysis by double aspiration of K₂EDTA blood through a 0.5 mL insulin syringe equipped with a very thin needle. The plasma was then separated from the blood cells by centrifugation at 2000 xg for 15 min at room temperature. A Beckman Coulter DxC 800 was used to measure the hemolysis index by direct spectrophotometry.ResultsCompared with matched nondiabetic controls, type 2 diabetic patients had a significantly increased mechanical fragility of erythrocytes (hemolysis index ratio 21 ± 13 vs. 14 ± 10, p = 0.02). Univariable linear regression analysis revealed that there was a strong positive association between percent hemolysis and fasting plasma glucose (r = 0.669, p < 0.001) and hemoglobin A1c (r = 0.549, p < 0.005) in type 2 diabetic subjects, but not in matched nondiabetic controls.ConclusionsOur data suggest that patients with type 2 diabetes have a significantly higher erythrocyte mechanical fragility than matched nondiabetic subjects, and that fasting plasma glucose is the strongest correlate of increased mechanical fragility of erythrocytes in this patients group.     

Magnesium intake, glucose and insulin serum levels in pre-school very-low-birth weight pre-term children

AimsTo evaluate cross-sectional associations between dietary magnesium intake and the metabolic pattern of very-low-birth-weight (VLBW, <1500 g) pre-term children, in pre-school years (>2 and < 6 years).Methods and resultsFifty-eight Italian children without major congenital malformations/conditions were enrolled; dietary intakes, clinical and (in 34 cases) laboratory characteristics were evaluated. Subjects with lower magnesium intake showed significantly higher fasting glucose, insulin and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) levels. At simple regression analysis, fasting glucose was significantly associated with magnesium intake (inversely) and catch-up growth (CUG). Fasting insulin and HOMA-IR values were inversely associated with intakes of magnesium and fibres, and directly with Body Mass Index (BMI) and CUG. In a multiple regression model, after adjusting for multiple confounders and fibre intake, magnesium intake was inversely associated with glucose (β = − 0.018; 95%CI −0.026 to −0.010), but not with insulin or HOMA-IR levels. In the same model, dietary fibres remained inversely associated with insulin (β = − 0.075; −0.14 to −0.008) and HOMA-IR levels (β = − 0.06; −0.11 to −0.01).ConclusionThese results suggest a significant association between reduced magnesium intake and fasting glucose, and between reduced fibre intake and insulin resistance and this is present even in earlier childhood, and independently of BMI and growth characteristics.     

Postprandial chylomicrons and adipose tissue lipoprotein lipase are altered in type 2 diabetes independently of obesity and whole-body insulin resistance

Background and aimsPostprandial lipoprotein abnormalities in type 2 diabetes are associated with insulin resistance. The role of other diabetes-related factors is still not clear. The aim of this study is to differentiate the effects of whole-body insulin resistance, obesity, and type 2 diabetes on postprandial dyslipidaemia and lipoprotein lipase (LPL) in adipose tissue.Methods and resultsTen subjects with obesity and diabetes (OD), 11 with obesity alone (O), and 11 normal-weight controls (C) – males, aged 26–59 years, with fasting normo-triglyceridaemia underwent measurements of cholesterol, triglycerides, apo B-48 and apo B-100 concentrations in plasma lipoproteins separated by density gradient ultracentrifugation before and after a fat-rich meal. Fasting and postprandial (6 h) LPL activity was determined in abdominal subcutaneous adipose tissue biopsy samples. Insulin sensitivity was measured by hyperinsulinaemic euglycaemic clamp. OD and O subjects had similar degrees of adiposity (BMI, waist circumference, fat mass) and insulin resistance (insulin stimulated glucose disposal and M/I). They also showed a similarly higher postprandial increase in large VLDL lipids (triglyceride incremental AUC 188 ± 28 and 135 ± 22 mg/dl·6 h) than C (87 ± 13 mg/dl·6 h, M ± SEM, p < 0.05). OD had an increased chylomicron response compared to O (triglyceride incremental AUC 132 ± 23 vs. 75 ± 14 mg/dl·6 h, p < 0.05). OD had significantly lower fasting and postprandial adipose tissue heparin-releasable LPL activity than O and C.ConclusionsIn insulin-resistant conditions of obesity, with and without diabetes, large VLDL are increased after a fat-rich meal. In addition, diabetic patients compared to obese subjects have an increased postprandial chylomicron response and a reduced adipose tissue LPL activity.     

Plasma HDL-cholesterol and triglycerides,but not LDL-cholesterol,are associated with insulin secretion in non-diabetic subjects

ObjectiveExperimental data support the notion that lipoproteins might directly affect beta cell function, however clinical data are sparse and inconsistent. We aimed at verifying whether, independently of major confounders, serum lipids are associated with alterations in insulin secretion or clearance non-diabetic subjects.MethodsCross sectional and observational prospective (3.5 yrs), multicentre study in which 1016 non-diabetic volunteers aged 30–60 yrs. and with a wide range of BMI (20.0–39.9 kg/m²) were recruited in a setting of University hospital ambulatory care (RISC study). Main outcome measures: baseline fasting lipids, fasting and OGTT-induced insulin secretion and clearance (measured by glucose and C-peptide modeling), peripheral insulin sensitivity (by the euglycemic clamp). Lipids and OGTT were repeated in 980 subjects after 3.5 years.ResultsLDL-cholesterol did not show independent associations with fasting or stimulated insulin secretion or clearance. After accounting for potential confounders, HDL-cholesterol displayed negative and triglycerides positive independent associations with fasting and OGTT insulin secretion; neither with insulin clearance. Low HDL-cholesterol and high triglycerides were associated with an increase in glucose-dependent and a decrease in non-glucose-dependent insulin secretion. Over 3.5 years both an HDL-cholesterol decline and a triglycerides rise were associated with an increase in fasting insulin secretion independent of changes in body weight or plasma glucose.ConclusionsLDL-cholesterol does not seem to influence any major determinant of insulin bioavailability while low HDL-cholesterol and high triglycerides might contribute to sustain the abnormalities in insulin secretion that characterize the pre-diabetic state.     

Fasting plasma C-peptide,glucagon stimulated plasma C-peptide,and urinary C-peptide in relation to clinical type of diabetes

Summary Many patients with Type 2 (non-insulin-dependent) diabetes mellitus are treated with insulin in order to control hyperglycaemia. We studied fasting plasma C-peptide, glucagon stimulated plasma C-peptide, and 24 h urinary C-peptide in relation to clinical type of diabetes in 132 insulin treated diabetic subjects. Patients were classified clinically as Type 1 (insulin-dependent) diabetic subjects in the presence of at least two of the following criteria: 1) significant ketonuria, 2) insulin treatment started within one year after diagnosis, 3) age of diagnosis 40 years, and 4) weight below 110% of ideal weight of the same age and sex. Eighty patients were classified as Type 1 and 52 as Type 2 diabetic subjects. A second classification of patients into 6 C-peptide classes was then performed. Class I consisted of patients without islet B-cell function. Class II-VI had preserved islet B-cell function and were separated according to the 20%, 40%, 60% and 80% C-peptide percentiles. The two classifications of patients were compared by calculating the prevalence of clinical Type 1 and Type 2 diabetes in each of the C-peptide classes. This analysis showed that patients with a fasting plasma C-peptide value <0.20 nmol/l, a glucagon stimulated plasma C-peptide value <0.32 nmol/l, and a urinary C-peptide value <3.1 nmol/l, or <0.54 nmol/mmol creatinine/24 h, or <5.4 nmol/24 h mainly were Type 1 diabetic patients; while patients with C-peptide levels above these values mainly were Type 2. At these limits the percentage, predictive value of positive tests as indicators of Type 2 diabetes were as follows: fasting C-peptide 83%, stimulated C-peptide 86%, and urinary C-peptide expressed as nmol/l 76%, as nmol/mmol creatinine/24 h 79%, and as nmol/24 h 78%. Similarly, the percentage predictive value of negative tests as indicators of Type 1 diabetes were as follows: fasting C-peptide 86%, stimulated C-peptide 88%, and urinary C-peptide expressed as nmol/l 79%, as nmol· mmol creatinine·24 h 81%, and as nmol/24 h 80%. If patients without detectable C-peptide were excluded, the predictive value of negative tests were as follows: fasting C-peptide 81%, stimulated C-peptide 88%, urinary C-peptide expressed as nmol/l 61%, as nmol/mmol creatinine/24 h 69%, and as nmol/24 h 64%. In conclusion, post glucagon C-peptide gives a good distinction between Type 1 and Type 2 diabetes mellitus in insulin treated diabetes while 24 h urinary C-peptide gives a less sensitive distinction between the clinical types of diabetes.     

The effects of adding group-based lifestyle counselling to individual counselling on changes in plasma glucose levels in a randomized controlled trial: the Inter99 study

AimThis study aimed to assess whether group-based lifestyle counselling offered to a high-risk population subgroup had any effect beyond individual multifactorial interventions on fasting plasma glucose (FPG) and 2-h plasma glucose (2hPG) changes.MethodsIn a population-based study of 6784 participants, 4053 were determined to be at high risk based on a risk estimate of ischaemic heart disease or the presence of risk factors (smoking, hypertension, hypercholesterolaemia, obesity, impaired glucose tolerance). Of these subjects, 90% were randomized to high-intensity intervention (group A) and 10% to low-intensity intervention (group B). All participants went through health examinations, risk assessments and individual lifestyle counselling. Participants in group A were further offered group-based lifestyle counselling. The intervention was repeated after 1 and 3 years. A total of 2738 participants free of diabetes at baseline (1999–2001) and with at least one FPG and/or 2hPG measurement during 5 years of follow-up were included in the analyses. Differences in changes of plasma glucose between groups A and B were analyzed using multilevel linear regression.ResultsFor FPG, crude 5-year changes were significantly different between the two groups (group A: ?0.003 mmol/L vs group B: ?0.079 mmol/L; P = 0.0427). After adjusting for relevant confounders, no differences in FPG changes were observed (P = 0.116). Also, no significant differences in the 5-year changes in 2hPG between the two groups were observed (group A: ? 0.127 mmol/L vs group B: ?0.201 mmol/L; P = 0.546).ConclusionOffering additional group-based intervention to a high-risk population subgroup had no clinical effects on changes in plasma glucose beyond those of individualized multifactorial interventions.     

Diabetes in Mozambique: prevalence, management and healthcare challenges

AimThe growing trend towards and deficient management of diabetes in Africa are important public-health challenges requiring surveillance. For this reason, this study aimed to assess the prevalence and awareness of diabetes in urban and rural Mozambique, and to describe its management.MethodsIn 2005, a representative sample of the national Mozambican adult population (n = 2343) was evaluated, according to the STEPwise approach to chronic disease risk factor surveillance (STEPS). Twelve-hour fasting blood glucose (FBG) was measured, using fingertip capillary whole blood, to estimate the prevalence of impaired fasting glucose (IFG; FBG ≥ 5.6 mmol/L and less than 6.1 mmol/L) and diabetes (FBG ≥ 6.1 mmol/L, or treatment with insulin and/or oral blood glucose-lowering drugs). Patients’ awareness and management of diabetes were assessed by questionnaire.ResultsThe prevalence of diabetes and IFG was 2.9% [95% confidence interval (95%CI): 1.8–4.0] and 2.5% (95%CI: 1.3–3.7), respectively. Diabetes was more frequent among urban dwellers (OR = 2.92, 95%CI: 1.45–5.86), mostly due to urban–rural differences in age, education, body mass index (BMI) and waist circumference (adjusted OR = 2.27, 95%CI: 0.83–6.26). In all, 13% of those with diabetes were aware of their condition, 10.9% had undergone glycaemia determination during the previous year, and 9% were being treated with oral blood glucose-lowering drugs and 3% with insulin.ConclusionDiabetes prevalence is low in Mozambique, but most diabetic patients were neither aware of their condition nor being treated pharmacologically, thus posing serious challenges to the provision of adequate care in an already disadvantageous context.     

Pancreatic β-cell function relates positively to HDL functionality in well-controlled type 2 diabetes mellitus

BackgroundHigh density lipoproteins (HDLs) have been implicated in glucose homeostasis. Among subjects with normal fasting glucose (NFG), impaired fasting glucose (IFG) and Type 2 diabetes mellitus (T2DM) we tested whether pancreatic β-cell function relates to HDL functionality, as determined by HDL anti-oxidative capacity and cellular cholesterol efflux to plasma.Subjects and methodsHDL anti-oxidative capacity (inhibition of LDL oxidation in vitro), cellular cholesterol efflux (the ability of plasma to stimulate cholesterol efflux out of cultured fibroblasts obtained from a single human donor), glucose and insulin were determined in fasting plasma samples from 37 subjects with NFG, 36 with IFG and 22 with T2DM (no glucose lowering drug or insulin treatment; HbA1c 6.0 ± 1.0%). Homeostasis model assessment was used to estimate pancreatic β-cell function (HOMA-β) and insulin resistance (HOMAir).ResultsHOMA-β was lowest, whereas HOMAir was highest in T2DM (P < 0.01 and P < 0.001 vs. NFG). HDL anti-oxidative capacity and cellular cholesterol efflux did not differ significantly according to glucose tolerance category. In univariate analysis and after controlling for HOMAir both HDL anti-oxidative capacity (P < 0.05) and cellular cholesterol efflux (P < 0.01) were positively correlated with HOMA-β in T2DM, but not in NFG and IFG. In age-, sex- and HOMAir-adjusted analyses, T2DM status interacted positively with HDL anti-oxidative capacity (P = 0.001) and cellular cholesterol efflux (P = 0.042) on HOMA-β. HbA1c interacted similarly with HDL functionality measures on HOMA-β.ConclusionsPancreatic β-cell function relates to pathophysiologically relevant measures of HDL function in T2DM, but not in NFG and IFG. Better HDL functionality may contribute to maintenance of β-cell function in subjects with well-controlled T2DM.     

sP-selectin plasma levels in obesity: association with insulin resistance and related metabolic and prothrombotic factors

Background and aimSoluble P-selectin (sP-sel) represents a marker of platelet activation. This study was addressed to investigate the associations of sP-sel plasma levels with anthropometric parameters, insulin resistance, and related metabolic and prothrombotic factors.Methods and results50 non-diabetic women, 17 with normal weight and 33 overweight and obese, aged 18–55 years, were examined. Measurements included body mass index (BMI), central fat accumulation (evaluated by waist circumference), systolic and diastolic blood pressure levels, fasting plasma concentrations of sP-sel, glucose, lipids (triglycerides, total cholesterol and HDL-cholesterol), insulin, and prothrombotic factors (plasminogen activator inhibitor-1, von Willebrand factor, fibrinogen), and insulin resistance (estimated by the homeostasis model assessment: HOMA_IR). Overweight and obese women had higher fasting plasma sP-sel concentrations compared to normal-weight controls (P < 0.05). sP-sel concentrations were positively correlated with BMI, HOMA_IR, systolic and diastolic blood pressure, fasting insulin, triglyceride and PAI-1 plasma levels (P < 0.05 for all the correlations). When a multiple regression analysis was performed, with P-sel as dependent variable and all the other parameters as independent variables, P-sel did not maintain a significant relationship with any of these variables.Conclusionss-P-selectin plasma concentrations are higher in overweight and obese insulin resistant subjects, thus possibly contributing to the cardiovascular risk of these patients. However, body fatness and insulin resistance are not independent determinants of fasting plasma sP-sel concentrations.     

Improvement in β-cell function after diet-induced weight loss is associated with decrease in pancreatic polypeptide in subjects with type 2 diabetes

ObjectiveThe aim of our study was to evaluate the effect of a lifestyle intervention program on β-cell function and to explore the role of gastrointestinal peptides in subjects with T2D.MethodsSubjects with T2D (n = 74) received 24 weeks of intervention: 12 weeks of slimming diet (? 500 kcal/day) and the subsequent 12 weeks of diet were combined with aerobic exercise. All subjects were examined at weeks 0, 12 and 24. β-cell function was assessed during standard meal tests. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution, and β-cell function was quantified with a mathematical model. Plasma concentrations of gastrointestinal peptides were measured in a fasting state and during hyperinsulinemia induced by hyperinsulinemic isoglycemic clamp.ResultsMean weight loss was 5.03 ± 4.38 kg (p < 0.001) in weeks 0–12. Weight did not change significantly in weeks 12–24. Both insulin secretion at the reference level and glucose sensitivity increased in weeks 0–12 (by 33% ± 54% and by 26% ± 53%, respectively, p < 0.001) and remained unchanged in weeks 12–24. Both fasting and hyperinsulinemic plasma concentrations of pancreatic polypeptide (PP) decreased in weeks 0–12 (p < 0.05 for both) and did not change significantly in weeks 12–24. Changes in insulin secretion at the reference level correlated negatively with plasma concentrations of PP during hyperinsulinemia (r = ? 0.36; p < 0.001). Changes in glucose sensitivity correlated negatively with changes in plasma concentrations of PP, both in fasting and during hyperinsulinemia (r = ? 0.2; p = 0.01 for both). The correlations remained significant after adjustment for changes in body-mass-index.ConclusionsAfter diet-induced weight loss, β-cell function improved in T2D subjects and remained unchanged after the addition of exercise. We demonstrate for the first time that these changes are associated with a decrease in PP secretion.     

Plasma proprotein convertase subtilisin-kexin type 9 does not change during 24h insulin infusion in healthy subjects and type 2 diabetic patients

PurposeProprotein convertase subtilisin–kexin type 9 (PCSK9) promotes low density lipoprotein (LDL) receptor degradation, thereby providing a key pathway for LDL metabolism. PCSK9 mRNA expression may be upregulated by insulin in murine models. Here we examined effects of exogenous hyperinsulinemia on plasma PCSK9 levels in humans without and with type 2 diabetes mellitus.MethodsA 24 h moderately hyperinsulinemic glucose clamp (30 mU/kg/h) was performed in 8 healthy men and 8 male type 2 diabetic patients. Plasma PCSK9 was measured using a sandwich enzyme-linked immunosorbent assay.ResultsPlasma LDL cholesterol and apolipoprotein B were lowered by insulin in healthy subjects and diabetic patients (P < 0.01 for all), whereas triglycerides were also decreased in healthy subjects (P < 0.01). Plasma PCSK9 levels remained unchanged in healthy subjects (median (interquartile range) change, ?23 (?63 to 25) %, P = 0.50) and in diabetic patients (change, 4 (?17 to 44) %, P = 0.20). Individual absolute and relative changes in LDL cholesterol, apolipoprotein B and triglycerides after 24 h of insulin were unrelated to changes in PCSK9 (P > 0.15 for all).ConclusionPlasma PCSK9 levels are not increased by exposure to moderate 24 h hyperinsulinemia in healthy and type 2 diabetic individuals.     

The effect of pioglitazone as add-on therapy to metformin or sulphonylurea compared to a fixed-dose combination of metformin and glibenclamide on diabetic dyslipidaemia

Background and aimsDiabetic dyslipidaemia contributes to the increased risk of cardiovascular disease in patients with Type 2 diabetes. This paper examines the effectiveness of adding pioglitazone to metformin or a sulphonylurea (SU) compared with a fixed-dose combination of metformin and glibenclamide on diabetic dyslipidaemia in patients with Type 2 diabetes.Methods and resultsPatients (n = 250) treated with metformin (≤3 g/day) or an SU as monotherapy at a stable dose for ≥3 months were randomised to receive either pioglitazone (15–30 mg/day) in addition to their metformin or SU, or a fixed-dose combination tablet containing metformin (400 mg) and glibenclamide (2.5 mg) [up to 3 tablets daily] for 6 months. Addition of pioglitazone tended to increase plasma high-density lipoprotein-cholesterol (HDL-C) [0.04 mmol/L; P = 0.051] at 6 months and significantly reduced plasma triglycerides (−0.25 mmol/L; P = 0.013) compared with baseline. Patients treated with metformin/glibenclamide for 6 months had reduced HDL-C (−0.09 mmol/L; P < 0.01) and no change in plasma triglyceride levels (0.03 mmol/L; P = 0.733). Both treatment regimes resulted in a similar level of glycaemic control.ConclusionThe beneficial effects of pioglitazone on diabetic dyslipidaemia may help combat the increased cardiovascular morbidity and mortality observed in patients with Type 2 diabetes while providing stable glycaemic control.