Insulin Sensitivity In Diabetic Patients Research Articles

Homeostasis Model Assessment for Insulin Resistance Mediates the Positive Association of Triglycerides with Diabetes.

Elevated circulating triglyceride levels have been linked to an increased risk of diabetes, although the precise mechanisms remain unclear. This study aimed to investigate whether low-density lipoprotein (LDL) cholesterol, homeostatic model assessment (HOMA) for insulin resistance, and C-reactive protein (CRP) served as mediators in this association across a sample of 18,435 US adults. Mediation analysis was conducted using the PROCESS Version 4.3 Macro for SPSS. Simple mediation analysis revealed that all three potential mediators played a role in mediating the association. However, in parallel mediation analysis, where all three mediators were simultaneously included, HOMA for insulin resistance remained a significant mediator (indirect effect coefficient, 0.47; 95% confidence interval [CI], 0.43-0.52; p < 0.05) after adjusting for all tested confounding factors. Conversely, LDL cholesterol (indirect effect coefficient, -0.13; 95% CI, -0.31-0.05; p > 0.05) and C-reactive protein (indirect effect coefficient, 0.01; 95% CI, -0.003-0.02; p > 0.05) ceased to be significant mediators. HOMA for insulin resistance accounted for 49% of the association between triglycerides and diabetes. In conclusion, HOMA for insulin resistance was the dominant mediator underlying the association between triglycerides and diabetes. Therefore, reducing triglyceride levels may hold promise for improving insulin sensitivity in diabetic patients.

Analysing uric acid levels to assess the effectiveness of dapagliflozin

Sodium-glucose cotransporter-2 inhibitors are an innovative diabetes treatment that lowers blood sugar levels without insulin. A growing body of evidence suggests that blood sugar levels are tightly correlated with uric acid levels in their blood and urine. To alleviate type 2 diabetes (T2DM) suffering, we tested dapagliflozin on serum and urinary uric acid levels of patients with T2DM and measured its efficacy in reducing uric acid levels. A study was conducted on 60 people with T2DM. Patients were treated with Dapagliflozin doses of 10mg daily for 3 months. Three months later, we measured body weight, fasting, and postprandial blood glucose levels, Hemoglobin A1C (HbA1c), serum lipids, renal function tests, routine urine, and serum uric acid. A number of clinical parameters of T2DM patients were compared to those of healthy subjects of the same age group. A comprehensive analysis of all parameters was conducted to evaluate dapagliflozin's impact. After 90 days of dapagliflozin treatment, serum uric acid levels dropped significantly from 9.0 to 8mg/dL in the dapagliflozin group, as well as uric acid percentage in urine changed from 16.1 to 23.6%. After three months of treatment, HbA1C levels decreased from 9.8% to 8.5%. Following treatment with dapagliflozin, the patients' Homeostatic Model Assessment for Insulin Resistance decreased to 4.0. Further, multivariate correlation analysis showed a correlation of serum uric acid with glycemic profile positively. In conclusion, dapagliflozin lowers uric acid levels and increases insulin sensitivity in diabetic patients to improve their glycemic control.

Effects of Exercise On Coronary Flow Reserve And Biochemical Parameters in Patients With Type 2 Diabetes Mellitus

The most important mortality and morbidity causes in diabetic patients are coronary, peripheral and cerebral diseases. The aim of our study was to noninvasively determine dysfunction in epicardial coronary arteries and microvascular circulation with measurement of coronary flow reserve using transthoracic echocardiography in patients with type 2 diabetes despite absence of ischemic symptoms, and to demonstrate the amelioration in endothelial functions, glycemic control and insulin resistance along with increase in coronary flow reserve after 8 weeks of regular exercise. 40 patients diagnosed with type 2 diabetes in Istanbul Facuty of Medicine, Department of Diabetes, who were on follow-up for at least three years due to diabetes, without ischemic symptoms and 20 healthy subjects took part in study. Basal values before exercise of diabetic patients who were included in the exercise program were compared with basal values of diabetic patients who did not exercise regularly. To summarize, regular exercise and physical activity are highly important in diabetic patients for primary and secondary protection against cardiovascular incidents. Physical activity increases insulin sensitivity in diabetic patients, and has many positive effects on glucose metabolism. It is the important way to decrease obesity and visceral fat tissue. There is evidence pointing out that regular exercise can defer or even prevent initiation of diabetes.

Modelling the effects of glucagon during glucose tolerance testing

BackgroundGlucose tolerance testing is a tool used to estimate glucose effectiveness and insulin sensitivity in diabetic patients. The importance of such tests has prompted the development and utilisation of mathematical models that describe glucose kinetics as a function of insulin activity. The hormone glucagon, also plays a fundamental role in systemic plasma glucose regulation and is secreted reciprocally to insulin, stimulating catabolic glucose utilisation. However, regulation of glucagon secretion by α-cells is impaired in type-1 and type-2 diabetes through pancreatic islet dysfunction. Despite this, inclusion of glucagon activity when modelling the glucose kinetics during glucose tolerance testing is often overlooked. This study presents two mathematical models of a glucose tolerance test that incorporate glucose-insulin-glucagon dynamics. The first model describes a non-linear relationship between glucagon and glucose, whereas the second model assumes a linear relationship.ResultsBoth models are validated against insulin-modified and glucose infusion intravenous glucose tolerance test (IVGTT) data, as well as insulin infusion data, and are capable of estimating patient glucose effectiveness (sG) and insulin sensitivity (sI). Inclusion of glucagon dynamics proves to provide a more detailed representation of the metabolic portrait, enabling estimation of two new diagnostic parameters: glucagon effectiveness (sE) and glucagon sensitivity (δ).ConclusionsThe models are used to investigate how different degrees of pax‘tient glucagon sensitivity and effectiveness affect the concentration of blood glucose and plasma glucagon during IVGTT and insulin infusion tests, providing a platform from which the role of glucagon dynamics during a glucose tolerance test may be investigated and predicted.

Postoperative evolution of insulin sensitivity in diabetic patients: leeve gastrectomy vs Roux-en-Y gastric bypass

The purpose of this study was to compare postoperative evolution of insulin sensibility in diabetic patients after the two most relevant bariatric surgeries nowadays, Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). A retrospective cohort study was conducted with type 2 diabetic patients, who underwent RYGB or SG from 2013 to 2018. The laboratory and anthropometric data was analyzed pre-surgery and during a 2-year follow-up. The tool chosen for this comparison was the HOMA2 nonlinear equations, calculated from fasting glycemia and blood insulin. The two surgical procedures were compared. There was significant difference between both evolutions in the first 6-months follow-up (p=0.029), but no difference was presented at the 1-year (p=0.053) or at the 2-year follow-up (p&gt;0.05). Therefore, there was no long-term difference between surgeries, which fuels discussions about their mechanisms of action and their relevance in the treatment of insulin resistance.

Whole food approach for type 2 diabetes prevention.

Diet is intimately associated with the risk of type 2 diabetes (T2D). Recently, attention has focused on the contributions of individual nutrients, food groups and eating patterns to the outcome of T2D. High consumption of coffee, whole grains, fruits and vegetables, and nuts are each independently associated with the reduced risk of T2D in high risk, glucose intolerant individuals. Experimental and clinical trials have given insight to the diverse mechanisms that may be responsible for the observed protective effects of certain foods on T2D, including nutrients, phytochemicals and dietary fiber, weight control, enhanced satiety and improvement in glucose tolerance and insulin sensitivity in diabetic patients. Elevated consumption of refined grains and sugar-sweetened beverages has shown to significantly elevate the risk of incident T2D. An overall healthy diet primarily comprising whole plant-based foods, together with regular physical activity and weight manage, could significantly reduce the risk of T2D. The present review consolidates current research and delineates major food groups shown to significantly influence risk of T2D. Documenting and quantifying the effects of diet on the outcome of T2D are of great scientific and public health importance as there is urgent need to implement dietary strategies to prevent and manage the outcome of T2D.

Relationship between HHV8 infection markers and insulin sensitivity in ketosis-prone diabetes

Background and objectivesPeripheral tissue resistance to insulin action is a characteristic of type 2 diabetes mellitus (T2DM). It has also been reported that some chronic viral infections can contribute to insulin resistance. Human herpesvirus (HHV)-8 infection has been detected in T2DM patients in previous studies. Our study investigated whether the presence of the virus is associated with insulin resistance in patients with ketosis-prone type 2 diabetes (KPD), as reported with other viruses. Research design and methodsA total of 11 insulin-free KPD patients positive (+) and seven patients who were negative (−) for HHV-8 infection were recruited; the latter had KPD that was well controlled (HbA1c=6.2±0.7%). A two-step euglycaemic–hyperinsulinaemic clamp test coupled with deuterated [6,6-2H2]glucose was used to assess insulin sensitivity, non-esterified fatty acid (NEFA) suppression and endogenous glucose production. ResultsIn KPD patients, whether HHV-8+ or HHV-8−, there were no differences in NEFA release, endogenous glucose production or insulin sensitivity (M value). ConclusionAsymptomatic HHV-8 infection does not appear to be associated with decreased insulin sensitivity in diabetic patients. These results should now be confirmed in a larger sample population.

Comparative evaluation of the therapeutic effect of metformin monotherapy with metformin and acupuncture combined therapy on weight loss and insulin sensitivity in diabetic patients.

Objective:Obesity induces insulin resistance (IR), the key etiologic defect of type 2 diabetes mellitus (T2DM). Therefore, an incidence of obesity-induced diabetes is expected to decrease if obesity is controlled. Although Metformin is currently one of the main treatment options for T2DM in obese patients, resulting in an average of 5% weight loss, adequate weight control in all patients cannot be achieved with Metformin alone. Thus, additional therapies with a weight loss effect, such as acupuncture, may improve the effectiveness of Metformin.Subjective:We designed this randomized clinical trial (RCT) to compare the effects of Metformin monotherapy with that of Metformin and acupuncture combined therapy on weight loss and insulin sensitivity among overweight/obese T2DM patients, to understand whether acupuncture plus Metformin is a better approach than Metformin only on treating diabetes. To understand whether acupuncture can be an insulin sensitizer and, if so, its therapeutic mechanism.Results:Our results show that Metformin and acupuncture combined therapy significantly improves body weight, body mass index (BMI), fasting blood sugar (FBS), fasting insulin (FINS), homeostasis model assessment (HOMA) index, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin, glucagon-like peptide-1 (GLP-1), resistin, serotonin, free fatty acids (FFAs), triglyceride (TG), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc) and ceramides.Conclusions:Consequently, Metformin and acupuncture combined therapy is more effective than Metformin only, proving that acupuncture is an insulin sensitizer and is able to improve insulin sensitivity possibly by reducing body weight and inflammation, while improving lipid metabolism and adipokines. As a result, electro-acupuncture (EA) might be useful in controlling the ongoing epidemics in obesity and T2DM.

Simple Self-Administered Method for Assessing Insulin Sensitivity in Diabetic Patients

Several methods have been proposed for evaluating a person’s insulin sensitivity from an oral glucose tolerance test (OGTT) and the euglycemic insulin clamp technique. However, none are easy or inexpensive to implement since the plasma insulin concentration, a key variable for assessing the insulin sensitivity index (ISI), is required to be clinically measured at specific times. Therefore, the purpose of this study is to develop a new ISI that can be easily and accurately obtained by patients themselves without costly, time-consuming, and inconvenient testing methods. This study proposes a simple self-administered testing method, simulated on a computerized model of type II diabetic patients, for estimating the ISI. The test involves a 75-g glucose ingestion and two injections of 10 mU/kg insulin. Blood glucose is measured 1 and 2 h later. The test was evaluated by using a previously developed diabetic-patient dynamic model. Fifteen sets of OGTT data from diabetic patients published in the literature were used for the model development. A simulation of the proposed self-administered test indicates that the proposed ISI correlates well with the ISI called M-value obtained from the gold standard but elaborate euglycemic hyperinsulinemic clamp (r = 0.927, p = 0.0045). The proposed ISI is considered to be easy to perform, time-saving, inexpensive, and accurate enough for clinical assessments.

Uncovering potential of Indonesian medicinal plants on glucose uptake enhancement and lipid suppression in 3T3-L1 adipocytes

Ethnopharmacological relevanceAs obesity is a key factor in the development of type 2 diabetes, lowering lipid accumulation in adipose tissues is as important as increasing insulin sensitivity in diabetic patients. The selected plant extracts used in this screen have been traditionally used in Indonesian medicine for the treatment of diabetes and its complications. Aim of the studyTo investigate the ability of the selected plants to both increase insulin sensitivity through the enhancement of glucose uptake after insulin induction in adipocytes and suppress lipid production in the same target cells. Materials and methodsDried Indonesian medicinal plants were extracted with 50% (v/v) aq. methanol. The extracts were dissolved in 50% DMSO when tested in 3T3-L1 adipocytes. The screening platform consists of insulin-induced glucose uptake, lipid accumulation, and cell viability. Initially, an enzymatic fluorescence assay was designed to demonstrate the enhancement of 2-deoxyglucose (2-DG) uptake after insulin induction. Different concentrations of the extracts that enhanced glucose uptake were subjected to lipid accumulation assay using Oil Red O staining. Potential extracts based on lipid suppression were subsequently assessed by CCK-8 cell viability assay to distinguish lipid reduction activity from cytotoxicity. ResultsOut of 59 plants, 13 plants demonstrated their ability to increase glucose uptake in 3T3-L1 adipocytes after insulin induction, and 4 of these plants׳ extracts suppressed lipid production of the cells. The CCK-8 assay results of those 4 plant extracts suggest that the lipid inhibition activity of Eurycoma longifolia Jack (root) and Piper nigrum L. (fruits) extracts is not attributed to their cytotoxicity in the adipose cells. Both of the plant extracts increased glucose uptake by more than 200% at 50μg/mL and suppressed lipid accumulation in a concentration-dependent manner. ConclusionsScreening of selected Indonesian medicinal plants has uncovered the potentials of E. longifolia Jack (root) and P. nigrum L. (fruits) with dual active functions, increasing insulin sensitivity through the enhancement of glucose uptake and reducing lipid accumulation in adipose cells. These findings suggest that the ability of both plants to suppress lipid production would provide additional benefits in the treatment of diabetes.

Diabetes phenomena can not affect serum ghrelin in obese individuals

Ghrelin is an acylated 28-amino-acid peptide plays role in glucose homeostasis, although the molecular basis of this relationship is not fully known yet. This study aimed to compare serum ghrelin between diabetes and no diabetes population and to determine relation between ghrelin with glucose in diabetes patient. For these purpose, fasting serum ghrelin, insulin, glucose and insulin sensitivity were measured in twelve adult obese men with or without type II diabetes. Independent student t test was used for between groups comparison. Pearson correlations were used to establish the relationship between serum ghrelin with glucose and insulin sensitivity in diabetic patients. A p-value less than 0.05 were considered statistically significant. No significant differences were observed in anthropometrical markers between two groups (p ≥ 0.05). Serum ghrelin was not difference between two groups (p = 0.385). Fasting glucose was significant higher (p < 0.001) and insulin sensitivity was significant lower (p < 0.001) in diabetes subjects. Positive correlation was observed between serum ghrelin and glucose concentration in studied patients (p = 0.006, r = 0.74). Based on these data, we conclude that diabetes phenomena can not affect serum ghrelin in obese individuals.

Effect of bariatric surgery on liver glucose metabolism in morbidly obese diabetic and non-diabetic patients

Bariatric surgery reduces weight and improves glucose metabolism in obese patients. We investigated the effects of bariatric surgery on hepatic insulin sensitivity. Twenty-three morbidly obese (nine diabetic and fourteen non-diabetic) patients and ten healthy, lean control subjects were studied using positron emission tomography to assess hepatic glucose uptake in the fasting state and during euglycemic hyperinsulinemia. Magnetic resonance spectroscopy was performed to measure liver fat content and magnetic resonance imaging to obtain liver volume. Obese patients were studied before bariatric surgery (either sleeve gastrectomy or Roux-en-Y gastric bypass) and six months after surgery. Insulin-induced hepatic glucose uptake was increased by 33% in non-diabetic and by 36% in diabetic patients at follow-up compared with baseline, but not totally normalized. The liver fat content was reduced by 76%, liver volume by 26% and endogenous glucose production by 19% in non-diabetic patients. The respective changes in diabetic patients were 73%, 24%, and 25%. Postoperatively, liver fat content and endogenous glucose production were almost normalized to lean controls, but liver volume remained greater than in control subjects. This study shows that bariatric surgery leads to a significant improvement in hepatic insulin sensitivity: insulin-stimulated hepatic glucose uptake was improved and endogenous glucose production reduced when measured, six-months, after surgery. These metabolic effects were accompanied by a marked reduction in hepatic volume and fat content. Overall, the gain in hepatic insulin sensitivity in diabetic patients was quite similar to non-diabetic patients for the same weight reduction.

Is there a role for HbA1c in predicting mortality and morbidity outcomes after coronary artery bypass graft surgery?: Table 1:

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was is there a role for HbA1c in predicting morbidity and mortality outcomes after coronary artery bypass surgery? Eleven studies presented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The studies presented analyse the relationship between preoperative HbA1c levels and postoperative outcomes following coronary artery bypass graft (CABG) in diabetic, non-diabetic or mixed patient groups. Four studies found significant increases in early and late mortality at higher HbA1c levels, regardless of a preoperative diagnosis of diabetes. One study demonstrated that 30-day survival outcomes were significantly worse in patients with previously undiagnosed diabetes and elevated HbA1c compared with those with good control [HbA1c >6%; odds ratio 1.53, confidence interval (CI) (1.24-1.91); P = 0.0005]. However, four studies of early mortality outcomes in diabetic patients only showed no significant differences between patients with normal and those with deranged HbA1c levels (P = 0.99). There were mixed reports on morbidity outcomes. Three studies identified a significant increase in infectious complications in patients with poorly controlled HbA1c, two of which were irrespective of previous diabetic status [deep sternal wound infection (P = 0.014); superficial sternal wound infection (P = 0.007) and minor infections (P = 0.006) in poorly controlled diabetics only]. Four studies presented outcomes for total length of stay (LOS). Three of these papers looked specifically at diabetic patients, of which two found no significant differences in length of stay between good and poor preoperative glycaemic control [LOS: P = 0.59 and 0.86 vs P < 0.001]. However, elevated HbA1c vs normal HbA1c was associated with prolonged stay in hospital and in intensive care unit (ICU) in patients irrespective of previous diabetic status [total LOS (P < 0.001)]. Elevated HbA1c levels were also a significant predictor of reduced intraoperative insulin sensitivity in diabetic patients (R = -0.527; P < 0.001). Furthermore, higher HbA1c levels were associated with a reduced incidence of postoperative atrial fibrillation (P = 0.001). We conclude that elevated HbA1c is a strong predictor of mortality and morbidity irrespective of previous diabetic status. In particular, the mortality risk for CABG is quadrupled at HbA1c levels >8.6%. Some studies have called into question the predictive value of HbA1c on short-term outcomes in well-controlled diabetics; however, long-term outcomes in this population have not been reported.

Relaxin, Insulin and Diabetes: An Intriguing Connection

Until recently, relaxin and insulin were grouped into the same hormone superfamily because of substantial biochemical homologies. This notion has then changed with the understanding that insulin and relaxin are ligands for different receptors and signal transduction systems, namely, tyrosine kinase and G-protein-coupled receptors respectively. As a matter of fact, relaxin does not mimic the metabolic effects of insulin. The biological effects of insulin are much more clearly delineated than those of relaxin, which is traditionally viewed as a reproductive hormone involved in the maternal adjustments of pregnancy. In the last decade, evidence has been accumulating that relaxin has major effects on the heart, blood vessels and the extracellular matrix within connective tissues. In particular, pertaining to the relationships between relaxin and diabetes, relaxin was shown to promote arterial and microvascular dilation, thereby increasing organ perfusion, counteract ischemic injury, improve adverse cardiac and vascular remodeling, and promote extracellular matrix turn-over, thereby exerting anti-fibrotic effects. Thus, relaxin could blunt or delay the vascular and organ complication of diabetes. Whether relaxin may also synergize with insulin to optimize blood glucose homeostasis remains an unconfirmed issue. However, there are clues in the literature which, if gathered, speak in favor of this perspective. Moreover, preliminary data suggest that exogenous relaxin administration may improve insulin sensitivity in diabetic patients. Considering that human recombinant relaxin is under study as a novel, promising drug for the treatment of heart failure, a broader knowledge of the possible beneficial effects of relaxin in diabetes and its complications can be of interest to the scientific community.

Improved insulin sensitivity by the angiotensin receptor antagonist irbesartan in patients with systolic heart failure: A randomized double-blinded placebo-controlled study

BackgroundImpaired insulin sensitivity is common in patients with chronic systolic heart failure (CHF) and contributes to symptomatic status and impaired prognosis. A specific metabolic effect to improve insulin sensitivity in diabetic patients has been reported for some but not all angiotensin II-receptor antagonists. We aimed to test the ancillary metabolic effect of irbesartan on insulin sensitivity in patients with CHF. Methods and participantsIn this placebo-controlled double-blinded study 36 non-diabetic patients with stable ischemic CHF (age 63±9years, peak VO2 16.6±4.8ml/kg/min, LVEF 32±9%) were randomized to irbesartan 300mg/d vs placebo on top of standard CHF therapy. Body composition (dual energy X-ray absorptiometry), clinical status, peripheral vasodilator capacity (plethysmography) and neuroendocrine and metabolic profiles were assessed. Primary endpoint was the change of whole body insulin sensitivity after 4months of treatment assessed by intravenous glucose tolerance testing and minimal modeling. ResultsInsulin sensitivity improved by 26% (p<0.001) in the irbesartan group, but not in the placebo group (treatment effect: 1.044min−1·μU·ml−1·104; 95%CI 0.45 to 1.64, p=0.0026). Treatment effects on systolic and diastolic blood pressure were −11 (95%CI −21 to −1)mmHg and −8 (95%CI −15 to −3)mmHg, respectively. Peripheral vasodilator capacity improved by 14% (p=0.016). Change in insulin sensitivity correlated with increased vasodilator capacity (R=0.47, p=0.021). Body composition and clinical status were not different after 4months of therapy. Also adiponectin, resistin, cytokine profile, and asymmetric dimethylarginine (ADMA) were not changed after this short-term intervention. ConclusionTherapy with irbesartan improved insulin sensitivity in patients with chronic heart failure. Improved peripheral vasodilator capacity may contribute to the metabolic effect. (Clinical trials identifier: NCT00347087).

Training With Joba Core Trainer For Obese Patients With Type 2 Diabetes

Physical activity (PA) and weight control are important in diabetes prevention and management. However, PA programs often fail to achieve optimal results in diabetic patients. The Joba® Core Trainer (JOBA) is an ergometric device, simulating horseback riding, which has been proved to improve insulin sensitivity in diabetic patients.1 PURPOSE: To assess if a training program with JOBA improves endothelial function, glycaemic control, and body mass in obese patients with type 2 diabetes mellitus (DM). METHODS: 24 obese pts. with DM were randomly allocated either to an Exercise (EX) group (3 sessions with JOBA/week for 12 weeks) or to usual care (C). Endothelial function, fasting glucose, insulin, glycated haemoglobin (HbA1C), body weight and composition were measured before and after the intervention. RESULTS: In the C group no significant changes were observed. In the EX group the endothelial-dependent (ED) dilation of the brachial artery significantly increased after training (4.6±3.2 vs. 7.0±3.6, p<0.045). Although fasting glucose was significantly reduced (142.0±41.9 vs. 118.7±40.8, p<0.001), HbA1C and insulin levels were not. Finally, Body Mass Index (BMI) and Fat Mass (FM) were not influenced by the intervention.TABLECONCLUSION: Training with JOBA resulted in a slight increase of ED vasodilation. Little effect, if any, was observed on glycaemic control. The training program did not affect body mass. It may be that the training intensity of JOBA exerts a favourable effect on vascular function, but it is not sufficient to influence metabolic control and body mass of obese pts. with DM. 1Kubota M et al. Mechanical horseback riding improves insulin sensitivity in elder diabetic patients. Diabetes Res Clin Pract. 2006;71:124-30

Relationship of Maximal Muscle Strength with Body Mass Index and Aerobics Capacity in Type 2 Diabetic Patients

Background: Combination fitness regimens (including aerobic and resistance exercises) are effective for improving cardio-respiratory fitness, reducing visceral fat and increasing insulin sensitivity in diabetic patients. The combination exercise intensity that a patient is capable of is limited by his or her aerobic capacity and one repetition maximum (1RM). We investigated the relationships between 1RM, aerobic exercise capacity and body mass index in patients with type 2 diabetes. Methods: A total of 177 (men: 85, women: 92) diabetic subjects with HbA1c ≤ 10% were enrolled. Muscle strength and 1RM were assessed bychest press (upper body) and l eg press (lower body). We assessed aerobic capacity by VO2max and muscle mass by bioimpedance analysis. Results: There was no correlation between 1RM and VO 2max in type 2 diabetic patients (upper: P = 0.122, lower: P = 0.138 for men, and upper: P = 0.952, lower: P = 0.570 for women). However, 1RM was significantly correlated with muscle mass both in men and women (upper: r = 0.493, P < 0.001, r = 0.315, P = 0.002 lower: r = 0.437 P < 0.001, r = 0.307, P =0.003, respectively). There was also a significant correlation between 1RM and BMI. In obese male subjects with BMI ≥ 25 kg/m 2 , we observed a significant correlation between muscle mass and BMI (r = 0.374, P = 0.032), but this correlation was not observed in women. Conclusion: Clinicians treating Korean type 2 diabetic subjects should recommend resistance exercise to their patients. In particular, obese women with diabetes may receive greater benefits by increasing muscle mass through resistance exercises. (Korean Diabetes J 33:511-517, 2009)

Treatment With Metoprolol Succinate, a Selective Beta Adrenergic Blocker, Lowers Blood Pressure Without Altering Insulin Sensitivity in Diabetic Patients

Insulin resistance is a risk factor for cardiovascular disease. Therapies to lower blood pressure should not decrease insulin sensitivity, especially among high-risk patients such as diabetics. This study examined the effect of the beta1-selective adrenergic receptor-blocking agent extended-release metoprolol succinate (ER metoprolol) on insulin sensitivity in type 2 diabetic patients with suboptimal blood pressure control. Diabetic patients with average blood pressure levels >130/85 mm Hg despite antihypertensive therapy had insulin sensitivity quantified by insulin clamp. ER metoprolol was then added to their ongoing therapy. Following 12 weeks of ER metoprolol plus other therapy, the insulin clamp study was repeated. There were no significant changes in measures of insulin sensitivity, plasma lipids, or hemoglobin A1c with use of ER metoprolol. When beta-blocker therapy is considered, it appears that this agent can be used to treat hypertension without adverse effects on insulin sensitivity in patients with type 2 diabetes, at least over the period of time treated.

Altered Promoter Recycling Rates Contribute to Dominant-Negative Activity of Human Peroxisome Proliferator-Activated Receptor-γ Mutations Associated with Diabetes

The transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma) plays an important role in regulating lipid and glucose metabolism and improves insulin sensitivity in diabetic patients when activated by thiazolidinedione drugs. Several loss-of-function mutations in PPARgamma have been identified that cause lipodystrophy and diabetes in humans. Because affected individuals are heterozygotes and have one normal PPARgamma allele, it is of interest to know whether these mutations act in a dominant-negative fashion to inhibit the activity of the wild-type (WT) receptor. Here we compare the molecular phenotypes of two previously identified PPARgamma mutations: P467L, reported to be dominant negative; and F388L, reported to be devoid of dominant-negative activity. We developed a competitive chromatin immunoprecipitation assay to measure the relative ability of mutant PPARgamma to compete with WT receptor for binding to a PPAR regulatory element (PPRE)-containing promoter. By determining the ratio of mutant and WT receptors bound to a PPRE over time, we estimated the relative promoter turnover rate of each receptor. This assay demonstrated that PPARgamma bearing the P467L had a reduced promoter turnover rate compared with the F388L receptor, and over time out-competed the WT receptor for promoter binding sites. We propose that the P467L receptor is dominant negative because in a cell containing both WT and mutant receptors, the majority of the PPAR-regulated promoters will be occupied by the transcriptionally defective mutant receptor. In contrast, the F388L mutation lacks dominant-negative activity because its more rapid promoter turnover rate prevented it from out-competing the WT receptor for promoter binding sites.

Pioglitazone Induces Mitochondrial Biogenesis in Human Subcutaneous Adipose Tissue In Vivo

Thiazolidenediones such as pioglitazone improve insulin sensitivity in diabetic patients by several mechanisms, including increased uptake and metabolism of free fatty acids in adipose tissue. The purpose of the present study was to determine the effect of pioglitazone on mitochondrial biogenesis and expression of genes involved in fatty acid oxidation in subcutaneous fat. Patients with type 2 diabetes were randomly divided into two groups and treated with placebo or pioglitazone (45 mg/day) for 12 weeks. Mitochondrial DNA copy number and expression of genes involved in mitochondrial biogenesis were quantified by real-time PCR. Pioglitazone treatment significantly increased mitochondrial copy number and expression of factors involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1alpha and mitochondrial transcription factor A. Treatment with pioglitazone stimulated the expression of genes in the fatty acid oxidation pathway, including carnitine palmitoyltransferase-1, malonyl-CoA decarboxylase, and medium-chain acyl-CoA dehydrogenase. The expression of PPAR-alpha, a transcriptional regulator of genes encoding mitochondrial enzymes involved in fatty acid oxidation, was higher after pioglitazone treatment. Finally, the increased mitochondrial copy number and the higher expression of genes involved in fatty acid oxidation in human adipocytes may contribute to the hypolipidemic effects of pioglitazone.