Insulin Reserve Research Articles

β- Cell function in a sample of Iraqi Patients with type 2 diabetes mellitus

Back ground: Type 2 diabetes is mostly due to impaired β-cell mass and dysfunction which expressed by Insulin secretion, sensitivity and resistance. Aim of study: to evaluate β- cell function in newly diagnosed and ongoing diabetics. Method: Eighty-eight subjects enrolled in this study with age range (30-59) years, (20) healthy individuals as controls group with mean age (42.95±9.80) years. (68) Diabetic Patients was divided into two groups, (26) newly diagnosed diabetic, mean age (45.81±8.16) years and (42) ongoing diabetics, mean age (49.33±6.64) year. "Fasting glucose", "lipid profile", "glycosylated hemoglobin", "C-peptide levels" were evaluated. Insulin secretion, sensitivity and resistance "HOMA B %", "HOMA S %"and "HOMA IR" respectively were estimated by "Homeostasis Model Assessment" "HOMA2 calculator program". Results: "Insulin secretion" and "sensitivity" were found to be lower (P 0.001) in both groups of diabetes than that controls, while a high level of insulin resistance in both diabetic groups than controls (P>0.0001)."C-peptide" level is higher in "newly diagnosed" diabetics than" ongoing diabetics" and controls (p˂0.0001). Conclusion: Patients with low c- peptide level has poor insulin reserve and may need insulin while patients with high level of c- peptide have good insulin reserve and not need insulin to control his blood glucose.

β- Cell function in a sample of Iraqi Patients with type 2 diabetes mellitus Isam Noori Salman

Back ground: Type 2 diabetes is mostly due to impaired β-cell mass and dysfunction which expressed by Insulin secretion, sensitivity and resistance.
 Aim of study: to evaluate β- cell function in newly diagnosed and ongoing diabetics.
 Method: Eighty eight subjects enrolled in this study with age range (30-59) years, (20) healthy individuals as controls group with mean age (42.95±9.80) years. (68) Diabetic Patients was divided into two groups, (26) newly diagnosed diabetic, mean age (45.81±8.16) years and (42) ongoing diabetics, mean age (49.33±6.64) year. "Fasting glucose", "lipid profile", "glycosylated hemoglobin", "C-peptide levels" were evaluated. Insulin secretion, sensitivity and resistance "HOMA B %", "HOMA S %"and "HOMA IR" respectively were estimated by "Homeostasis Model Assessment" "HOMA2 calculator program".
 Results:"Insulin secretion" and "sensitivity" were found to be lower (P 0.001) in both groups of diabetes than that controls, while a high level of insulin resistance in both diabetic groups than controls (P>0.0001)."C-peptide" level is higher in "newly diagnosed" diabetics than" ongoing diabetics" and controls (p˂0.0001).
 Conclusion: Patients with low c- peptide level has poor insulin reserve and may need insulin while patients with high level of c- peptide have good insulin reserve and not need insulin to control his blood glucose.

Long-lasting Glucagon-like Peptide 1 Analogue Exendin-4 Ameliorates the Secretory and Synthetic Function of Islets Isolated From Severely Scalded Rats.

The aim of this article was to observe the intracellular insulin content of islets isolated from severely scalded and Exendin-4-treated rats and to evaluate the stimulation of insulin mRNA synthesis and secretion by β cells at different glucose concentrations and during different periods of time. A 50% TBSA full-thickness scalded rat model was used. Rats were treated with Exendin-4, followed by islet isolation and functional measurements. Serum was collected for detection of serum insulin, glucose, and glucagon levels. Intracellular insulin content was determined by transmission electron microscopy. Isolated islets were incubated with different glucose concentrations for 1 or 24 hours to assess the effect of scalding with or without Exendin-4 treatment on functional parameters. Insulin secretion was analyzed by enzyme-linked immunosorbent assay. Intracellular insulin and proinsulin content were analyzed by immunoprecipitation. Islet preproinsulin mRNA expression was examined by real-time polymerase chain reaction. Transmission electron microscopy analyses showed that severe thermal injury significantly reduced the number of insulin granules per micrometer2. Insulin secretion and intracellular insulin and proinsulin levels were markedly reduced in islets stimulated with different glucose concentrations; chronic high-glucose-stimulated islet preproinsulin mRNA expression was also impaired. Exendin-4 treatment after thermal trauma improved the number of intracellular insulin granules. Exendin-4 improved both insulin secretion and intracellular insulin reserves under different glucose stimulation conditions. Islet insulin mRNA expression was also restored by Exendin-4 treatment. Exendin-4 can restore the islet β cell insulin reserve following severe scald injury and may also improve insulin secretion, insulin reserve, and mRNA expression in islet β cells.

Relation of Muscle Indices with Metabolic Parameters and C-Peptide in Type 2 Diabetes Mellitus.

To assess the relation between bioimpedance measurements and metabolic parameters and C-peptide in patient with type 2 diabetes mellitus (DM). Cross-sectional study. Kartal Dr Lutfi Kirdar Training and Research Hospital, Pendik Kaynarca Diabetes Center, Exercise and Metabolism Unit, between January and March 2015. Patients with DM, aged less than 65 years, were assessed for bioimpedance analysis, fasting plasma glucose (FPG), HbA1c, C-peptide levels, triglyceride levels, LDL-cholesterol, and HDL-cholesterol levels. Skeletal muscle index, total muscle index, skeletal muscle percentage, and total muscle percentage were used for muscle-related analyses. Mann-Whitney U-test or independent t-test were used to compare differences between two independent groups. Pearson correlation test or Spearman correlation test were used to find out correlation between variables. Atotal of 359 DM patients were enrolled in the study. Mean age was 51.6 ±8.0 years, and 278 (77.7%) of the participants were females. After adjusting age and gender variables, there was no relation between muscle-related measurements and FPG, triglyceride, LDL-cholesterol (p>0.05). However, there was muscle-related indexes (MRI) positively correlation with C-peptide and inversely associated with HDL-cholesterol (p<0.05). Muscle-related indices positively correlated with C-peptide, which showed endogenous insulin reserve.

Evaluation of serum c-peptide levels in type 2 diabetics in Punjabi population

Background: Diabetes mellitus is a chronic metabolic and endocrine disorder characterized by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action or both. It is a major cause of mortality and morbidity worldwide. Human insulin and c-peptide are synthesized as a single polypeptide chain known as Proinsulin in the pancreatic beta cells. Serum insulin measurement gives a wrong value of insulin secretion, because insulin after its secretion into the portal vein, passes through the liver where approximately 50% of the delivered insulin is extracted. The measurement of C-peptide, thus provides a better index of endogenous insulin production and pancreatic beta cell function than insulin measurements.Methods: The present study was conducted on 100 adult patients of type 2 diabetes mellitus presenting in OPD and emergency or admitted in Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar. Type 1 diabetic patients, pregnant females with diabetes, patients presenting with acute infections, septicaemia, patients with acute or chronic pancreatitis, patients with pancreatic carcinoma were excluded from the study. In this study C-Peptide levels were estimated by DRG C-peptide ELISA method.Results: In our study, 38% patients had adequate insulin reserve (Normal C-peptide levels). Only 2% patients had poor insulin reserve (C-peptide levels below normal). 60% patients had c peptide levels more than normal, indicating insulin resistance. Increase in fasting c-peptide levels were associated with increased fasting plasma glucose (due to insulin resistance). A positive correlation exists in our study with r value of 0.523.Conclusions: As majority of patients with elevated FBS and fasting c-peptide were obese, our study infers that obese are more insulin resistant than non-obese. Since c-peptide levels assess the endogenous insulin reserve, it will also be helpful to alter the treatment modality based on it. So, routine c-peptide testing should be done in patients with poor glycaemic control to modify treatment modality accordingly.

Type 1 versus type 2 diabetes: is it time for a change?

Type 1 versus type 2 diabetes: is it time for a change?

Considerations on glycaemic control in older and/or frail individuals with diabetes and advanced kidney disease.

The increasing prevalence of chronic kidney disease (CKD) and diabetes over the last decade has resulted in increasing numbers of frail older patients with a combination of these conditions. Current treatment guidelines may not necessarily be relevant for such patients, who are mostly excluded from the trials upon which these recommendations are based. There is a paucity of data upon which to base the management of older patients with CKD. Nearly all current guidelines recommend less-tight glycaemic control for the older population, citing the lack of proven medium-term benefits and concerns about the high short-term risk of hypoglycaemia. However, reports from large landmark trials have shown potential benefits for both microvascular and macrovascular complications, though the relevance of these findings to this specific population is uncertain. The trials have also highlighted potential alternative explanations for the hazards of intensive glycaemic control. These include depression, low endogenous insulin reserve, low body mass index and side effects of the medication. Over the last few years, newer classes of hypoglycaemic drugs with a lower risk of hypoglycaemia have emerged. This article aims to present a balanced view of advantages and disadvantages of intense glycaemic control in this group of patients, which we hope will help the clinician and patient to come to an individualized management approach.

The Effects of Blood Glucose Regulation in Omentin-1 Levels among Diabetic Patients.

Objectives: Omentin-1, an adipocytokine that increases the insulin sensitivity, has been determined to be reduced in patients with insulin resistance, impaired glucose tolerance, and Type-2 diabetes mellitus. In this study, we have investigated the alterations in Omentin-1 levels with the blood glucose regulation in diabetic patients having poor glycemic control. By this way, we aimed to determine the role of Omentin-1 as a marker in follow-up and monitoring progression of diabetes. Methods: Totally 58 patients with type 2 diabetes mellitus, older than 18 years of age who were having poor glycemic control (HbA1c≥9) were included in this study. In the first visit, all clinical and biochemical parameters of patients were recorded. After baseline evaluation, the patients were advised life style changes, and their medical treatment was determined individually according to the recommendations of the American Diabetes Association guidelines. At the end of the third month patients were re-evaluated. Serum Omentin-1 levels were measured with ELISA. Results: In patients using only oral antidiabetic agents, after exchanging the treatment with insulin, on 3rd month of treatment, there was a significant decrease in serum C-peptide and Omentin-1 levels compared with the initial results (p=0.034, p=0.048, respectively). On the other hand, in patients using insulin treatment from the beginning of the study, there was not any significant alterations in serum C-peptide or Omentin-1 levels compared with the initial results (p>0.05). Conclusions: Serum Omentin-1 levels may change with insulin and metformin treatments in Type-2 diabetic patients. In patients with poor glycemic control, Omentin-1 levels do not change with the regulation of blood glucose levels. A decrease in Omentin-1 and C-peptide levels has been determined after the initiation of insulin therapy. This suggests that, Omentin-1 levels are closely associated with the endogenous insulin reserve and may be used in follow-up of patients.

Clinical and metabolic profile of patients with latent autoimmune diabetes in adults in specialized care in Madrid

ObjectiveTo report the clinical characteristics of patients with latent autoimmune diabetes in adults (LADA), and to ascertain their metabolic control and associated chronic complications. MethodsPatients with DM attending specialized medical care in Madrid who met the following criteria: age at diagnosis of DM >30years, initial insulin independence for at least 6months and positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis, associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic control, and presence of chronic complications were analyzed. ResultsNumber of patients; 193; 56% females. Family history of DM: 62%. Age at DM diagnosis: 49years. Delay in confirmation of LADA: 3.5years. Insulin-independence time: 12months. Baseline serum C-peptide levels: 0.66ng/ml. Basal-bolus regimen: 76.7%. Total daily dose: 35.1U/day, corresponding to 0.51U/kg. With no associated oral antidiabetic drugs: 33.5%. Other autoimmune diseases: 57%. Fasting plasma glucose: 160.5mg/dL. HbA1c: 7.7%. BMI: 25.4kg/m2 (overweight, 31.5%; obesity, 8%). Blood pressure: 128/75. HDL cholesterol: 65mg/dL. LDL cholesterol: 96mg/dL. Triglycerides: 89mg/dL. Known chronic complications: 28%. ConclusionsRecognition of LADA may be delayed by several years. There is a heterogeneous pancreatic insulin reserve which is negative related to glycemic parameters. Most patients are poorly controlled despite intensive insulin therapy. They often have overweight, but have adequate control of BP and lipid profile and a low incidence of macrovascular complications.

Perfil clínico y metabólico de pacientes con diabetes tipo LADA atendidos en atención especializada en la comunidad de Madrid

ObjectiveTo report the clinical characteristics of patients with latent autoimmune diabetes in adults (LADA), and to ascertain their metabolic control and associated chronic complications. MethodsPatients with DM attending specialized medical care in Madrid who met the following criteria: age at diagnosis of DM >30years, initial insulin independence for at least 6months and positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis, associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic control, and presence of chronic complications were analyzed. ResultsNumber of patients; 193; 56% females. Family history of DM: 62%. Age at DM diagnosis: 49years. Delay in confirmation of LADA: 3.5years. Insulin-independence time: 12months. Baseline serum C-peptide levels: 0.66ng/ml. Basal-bolus regimen: 76.7%. Total daily dose: 35.1U/day, corresponding to 0.51U/Kg. With no associated oral antidiabetic drugs: 33.5%. Other autoimmune diseases: 57%. Fasting plasma glucose: 160.5mg/dL. HbA1c: 7.7%. BMI: 25.4kg/m2 (overweight, 31.5%; obesity, 8%). Blood pressure: 128/75. HDL cholesterol: 65mg/dL. LDL cholesterol: 96mg/dL. Triglycerides: 89mg/dL. Known chronic complications: 28%. ConclusionsRecognition of LADA may be delayed by several years. There is a heterogeneous pancreatic insulin reserve which is negative related to glycemic parameters. Most patients are poorly controlled despite intensive insulin therapy. They often have overweight, but have adequate control of BP and lipid profile and a low incidence of macrovascular complications.

Calculated Daily Insulin Dosages Overestimate Prescribed Insulin Doses in Type 2 Diabetes: A Primary Care Database Study.

The aim was to compare the prescribed and calculated daily insulin dosages based on prescription data in type 2 diabetes patients in a general practice database. A total of 17 782 type 2 diabetes patients (age: 70.0 ± 11.5 years; 52% males; 16% diabetologist care) with ≥2 insulin prescriptions from 834 practices were analyzed (Disease Analyser: 01/2011-12/2015). Prescribed daily dosage (PDD) (physician documentation) and calculated daily dose (CDD) (pack size × strength × volume / days between 2 prescriptions) were calculated for short-acting, long-acting, and premixed insulins. PDD and CDD were compared using paired t-tests. Linear regression models assessed the associations of insulin dosage difference (CDD-PDD) with age, sex, diabetologist care, private health insurance, obesity, HbA1c, hypertension, hyperlipidemia, macro- and microvascular complications. Mean [SD] CDDs were higher than PDDs for short-acting (52 [28] vs 48 [26] units/day), long-acting (30 [20] vs 24 [15] units/day), and premixed (46 [26] vs 40 [21] units/day) insulins (all P < .05). In regression models, age (per year) was associated with higher CDD-PDD differences (+0.11, +0.04, +0.10; P < .01) for short-, long-acting, and premixed insulins, respectively. Diabetologist care was related to lower differences (-2.92, -1.02, -3.65; all P < .05). HbA1c was associated with higher differences in long-acting and premixed insulins, but was related to a lower difference in short-acting insulins (all P < .05). CDD in primary care database studies substantially overestimate the PDD (8-25%). Age, diabetologist care, and glycemic control were related to CDD-PDD differences. Priming and safety shots with pens, dosing errors, or the accumulation of insulin reserves by patients may be underlying reasons.

Clinical characteristics of type 1 diabetes mellitus in Taiwanese children aged younger than 6 years: A single-center experience.

Cases of type 1 diabetes mellitus in children aged younger than 6 years in Taiwan has increased in the past 10 years. This retrospective study aimed to review the management experience of such patients in a single center. From January 2004 to June 2015, 52 newly diagnosed diabetic children younger than 6 years who had regular follow-up for >1 year were enrolled, as well as 94 older diabetic children for comparison. Their medical records were thoroughly reviewed. The most common symptoms and signs were polyuria, polydipsia, dry lips, weight loss, and nocturia. Among the children younger than 6 years, 87% had ketoacidosis upon diagnosis-significantly higher than that of the older age group-and 88% had at least one islet cellautoantibody detected. Their serum C-peptide levels were significantly lower and the frequency of insulin autoantibodies detected was significantly higher compared with the older age group (37% vs. 10%). The remission rate of the young diabetic patients was significantly lower than that of the older age group (40% vs. 59%), but there was no difference in time of onset and duration of remission between the two groups. Autoimmune destruction of pancreatic β-cells is an important cause of type 1 diabetes mellitus in Taiwanese children aged younger than 6 years. These patients usually have a low insulin reserve and severe ketoacidosis upon diagnosis. A high index of suspicion in the presence of classic symptoms of diabetes in young children is important to prevent complications.

Hyperglucagonemia in an animal model of insulin- deficient diabetes: what therapy can improve it?

BackgroundIntra-islet insulin contributes to alpha-cell suppression. Akita mice carry a toxic-gain-of- function Ins2 gene mutation encoding proinsulin-C(A7)Y, similar to that described in human Mutant Ins-gene induced Diabetes of Youth, which decreases intra-islet insulin. Herein, we examined Akita mice for examination of circulating insulin and circulating glucagon levels. The possibility that loss of intra-islet suppression of alpha-cells, with increased circulating glucagon, contributes to diabetes under conditions of intra-islet insulin deficiency, raises questions about effective treatments that may be available.MethodsBlood glucose, plasma insulin, C-peptide I, C-peptide II, and glucagon were measured at various times during development of diabetes in Akita mice. We also used Akita- like hProC(A7)Y-CpepGFP transgenic mice in Ins2 +/+, Ins2 +/− and Ins2 −/− genetic backgrounds (providing animals with greater or lesser defects in islet insulin production, respectively) in order to examine the relative abundance of immunostainable intra-islet glucagon-positive and insulin-positive cells. Similar measurements were made in Akita mice. Finally, the effects of treatment with insulin, exendin-4, and leptin on blood glucose were then compared in Akita mice.ResultsInterestingly, total insulin levels in the circulation were not frankly low in Akita mice, although they did not rise appropriately with the onset of hyperglycemia. By contrast, in severely diabetic Akita mice at 6 weeks of age, circulating glucagon levels were significantly elevated. Additionally, in Ins2 +/− and Ins2 −/− mice bearing the Akita-like hProC(A7)Y-CpepGFP transgene, development of diabetes correlated with an increase in the relative intra-islet abundance of immunostainable glucagon-positive cells, and a similar observation was made in Akita islets. In Akita mice, whereas a brief treatment with exendin-4 resulted in no apparent improvement in hyperglycemia, leptin treatment resulted in restoration of normoglycemia. Curiously, leptin treatment also suppressed circulating glucagon levels.ConclusionsLoss of insulin-mediated intra-islet suppression of glucagon production may be a contributor to hyperglycemia in Akita mice, and leptin treatment appears beneficial in such a circumstance. This treatment might also be considered in some human diabetes patients with diminished insulin reserve.

Relationship between lipoprotein (a) and micro/macro complications in type 2 diabetes mellitus: a forgotten target.

ObjectivesIncreased lipoprotein (a) serum concentrations seems to be a cardiovascular risk factor; this has not been confirmed in extracoronary atherosclerosis complications. We therefore wished to gain a deeper insight into relationship between the plasma concentrations of lipoprotein (a) and the micro- and macro-vascular complications of type 2 diabetes mellitus and to identify possible differences in this association.MethodsThis is a descriptive observational cross-sectional study. Two-hundred and seventeen elderly patients with type 2 diabetes mellitus were included from the internal medicine outclinic. Anthropometric data, analytical data (insulin reserve, basal and postprandial peptide C, glycosylated hemoglobin, renal parameters, lipid profile and clinical data as hypertension, obesity, micro- and macrovascular complications were collected.ResultsPatients were grouped according to the type 2 diabetes mellitus time of evolution. The mean plasma concentration of lipoprotein (a) was 22.2 ± 17.3 mg/dL (22.1 ± 15.9 mg/dL for males, and 22.1 ± 18.4 mg/dL for females). Patients with hypertension, coronary heart disease, cerebrovascular accident, microalbuminuria and proteinuria presented a statistically significant increased level of lipoprotein (a). Similarly, the patients with hyperlipoprotein (a) (≥ 30 mg/dL) presented significantly increased levels of urea and total cholesterol. In the multivariate regression model, the level of lipoprotein (a) is positively correlated with coronary heart disease and diabetic nephropathy (P < 0.01 and P < 0.005, respectively).ConclusionsThe elevation of plasma levels of lipoprotein (a) are associated with the development of coronary heart disease and diabe tic nephropathy. Therefore, we consider that the determination of lipoprotein (a) may be a prognostic marker of vascular complications in patients with type 2 diabetes mellitus.

Declining ß-cell function is associated with the lack of long-range negative correlation in glucose dynamics and increased glycemic variability: A retrospective analysis in patients with type 2 diabetes

ObjectiveTo determine whether characteristics of glucose dynamics are reflections of β-cell function or rather of inadequate diabetes control. Materials/methodsWe analyzed historical liquid meal tolerance test (LMTT) and continuous glucose monitoring (CGM) data, which had been obtained from 56 non-insulin treated type 2 diabetic outpatients during withdrawal of antidiabetic drugs. Computed CGM parameters included detrended fluctuation analysis (DFA)-based indices, autocorrelation function exponent, mean amplitude of glycemic excursions (MAGE), glucose SD, and measures of glycemic exposure. The LMTT-based disposition index (LMTT-DI) calculated from the ratio of the area-under-the-insulin-curve to the area-under-the-glucose-curve and Matsuda index was used to assess relationships among β-cell function, glucose profile complexity, autocorrelation function, and glycemic variability. ResultsThe LMTT-DI was inverse linearly correlated with the short-range α1 and long-range scaling exponent α2 (r = −0.275 and −0.441, respectively, p < 0.01) such that lower glucose complexity was associated with better preserved insulin reserve, but it did not correlate with the autocorrelation decay exponent γ. By contrast, the LMTT-DI was strongly correlated with MAGE and SD (r = 0.625 and 0.646, both p < 0.001), demonstrating a curvilinear relationship between β-cell function and glycemic variability. On stepwise regression analyses, the LMTT-DI emerged as an independent contributor, explaining 20, 38, and 47% (all p < 0.001) of the variance in the long-range DFA scaling exponent, MAGE, and hemoglobin A1C, respectively, whereas insulin sensitivity failed to contribute independently. ConclusionsLoss of complexity and increased variability in glucose profiles are associated with declining β-cell reserve and worsening glycemic control.

Improved islet function is associated with anti-inflammatory, antioxidant and hypoglycemic potential of cinnamaldehyde on metabolic syndrome induced by high tail fat in rats

Cinnamon is used in traditional medicine and foods. In this study the protective effects of cinnamaldehyde, one of the most abundant compound of cinnamon against metabolic syndrome induced by high fat diet, were investigated. To induce metabolic syndrome, male Wistar rats were given high fat diet for 16 weeks. Cinnamaldehyde was administrated orally (143.8 µmol/kg body weight) concomitant with high fat feed. Changes in islet morphology, lipid profile, TNF-α, TBARS, insulin resistance were analyzed. Metabolic syndrome was induced by high fat diet. Cinnamaldehyde reversed this process and significantly reduced insulin secretion and content in isolated islets of high fat diet. Beta cell enlargement, TNF-α and TBARS significantly increased with high fat diet, cinnamaldehyde restored both to the control level. Cinnamaldehyde prevented all symptoms of metabolic syndrome by improving oxidative and inflammatory conditions in pancreatic islets with no effect on insulin secretion but by enhancing insulin reserve and preventing beta cell damage.

Islets Β Cell Response and Glucose Homeostasis in Low Body Weight Type 2 Diabetes

Introduction: Low body weight Type 2 Diabetes Mellitus (LB T2 DM) is not a distinct clinical entity that is related clinically or pathophysiologically to latent autoimmune diabetes in adults (LADA) nor to Type 1DM, have absence of markers for autoimmune destruction of β-cells and good insulin and C-peptide reserve for a prolonged period of life. They constitute an independent variant of Type 2 DM with inherent peculiarities of insulin kinetics in the liver along with altered profile and behavior of key enzymes related to carbohydrate metabolism which are marked by excess extraction of insulin in the hepatic bed, hyperactive cytochrome system and non-suppressible glucokinase activity. These peculiarities are reflected in the peripheral circulation as low circulating insulin levels and severe persistent hyperglycemia despite fairly preserved β cell reserve for insulin. Peripheral persistent hyperglycemia could be the likely cause for higher prevalence of peripheral neuropathy, infections and endothelial cell dysfunction. In view of higher prevalence of infective complications and coexistent severe hyperglycemia, many of these diabetics may not respond to Oral Anti diabetic Drugs (OAD) adequately at the initiation of therapy. However, due to existence of insulin resistance and good β-cell reserve for insulin, despite of lean habitus, glucose homeostasis and normo glycemia is often maintained with OAD for long periods of life, as may be comparable with any other phenotype of Type 2 DM. The insulin resistance observed in LB T2 DM is not related to anthropometric parameters like central obesity and Waist Hip Ratio (WHR). Conclusion: LB T2DM are variant of classical (obese) Type 2 DM where the lean habitus is neither consequent to under nutrition, having low circulating insulin levels, nor due to autoimmune β-cell destruction but have inherent metabolic aberrations in hepatic bed extracting more insulin causing low circulating insulin levels. They do have peripheral insulin resistance. The management although akin to classical Type 2 DM, biguanides are avoided, the complications profile are visibly different from the Type 2 DM seen in the West.

Omentum Is Better Site Than Kidney Capsule for Growth, Differentiation, and Vascularization of Immature Porcine β-Cell Implants in Immunodeficient Rats

BackgroundRapid revascularization of islet cell implants is important for engraftment and subsequent survival and function. Development of an adequate vascular network is expected to allow adaptive growth of the β-cell mass. The present study compares omentum and kidney capsule as sites for growth and differentiation of immature β-cell grafts.MethodsPerinatal porcine islet cell grafts were implanted in omentum or under kidney capsule of nondiabetic nude rats. Implants were compared over 10 weeks for their respective growth, cellular composition, number and size of β cells, their proliferative activity, and implant blood vessel density.ResultsIn both sites, the β-cell volume increased fourfold between weeks 1 and 10 reflecting a rise in β-cell number. In the omental implants, however, the cellular insulin reserves and the percent of proliferating cells were twofold higher than in kidney implants. In parallel, the blood vessel density in omental implants increased twofold, reaching a density comparable with islets in adult pig pancreas. A positive correlation was found between the percent bromodeoxyuridine-positive β cells and the vessel density.ConclusionsGrowth of the β-cell volume proceeds similarly in the omentum and under the kidney capsule. However, the omentum leads to higher insulin reserves and an increased pool of proliferating cells, which might be related to a more extended vascular network. Our observations support the omentum as an alternative site for immature porcine islet cells, with beneficial effects on proliferation and implant revascularization.

Metabolic surgery for type 2 diabetes with BMI

Is bariatric surgery as primary therapy for type 2 diabetes mellitus (T2DM) with body mass index (BMI) <35 kg/m2 justified? Open-label studies have shown that bariatric surgery causes remission of diabetes in some patients with BMI <35 kg/m2. All such patients treated had substantial weight loss. Diabetes remission was less likely in patients with lower BMI than those with higher BMI, in patients with longer than shorter duration and in patients with lesser than greater insulin reserve. Relapse of diabetes increases with time after surgery and weight regain. Deficiencies of data are lack of randomized long-term studies comparing risk/benefit of bariatric surgery to contemporary intensive medical therapy. Current data do not justify bariatric surgery as primary therapy for T2DM with BMI <35 kg/m2.

New Avenue in Islet Transplantation by Macroencapsulation and Islet Pre-Treatment with Growth Hormone Releasing Hormone Agonist

Introduction: Islet transplantation is a feasible therapeutic alternative for metabolically labile patients with type 1 diabetes. The primary therapeutic target is stable glycemic control and prevention of complications by reconstitution of endogenous insulin secretion. However, gradual loss in graft function over time due to insufficient oxygenation and inflammatory reactions, and chronic need for immunosuppression limit the outcome and the indication for islet transplantation. Methods: Here we present the approach of utilization of a macrochamber specially engineered for islet transplantation. The subcutaneous implantable device allows for controlled and adequate oxygen supply and provides immunological protection. In an isogeneic (n=16) and allogeneic (n=7) rodent model, pancreatic islets were embedded in alginate, integrated into the chamber-system and transplanted into Streptozotocin-induced diabetic rats. In addition, islets were pre-treated with growth hormone-releasing hormone (GHRH) agonist, JI-36. Prior to transplantation, islets were characterized for morphology and function by glucose stimulated insulin release, determination of oxygen consumption rate and immunohistochemistry. During the follow-up period of up to 90 days, blood glucose levels were measured daily and animals were subjected to an intravenous glucose tolerance test. The islet graft was removed at the end of the observation period to ensure recurrence of diabetes and enabling post-explantation assessment of the islet graft and the chamber surrounding tissue. Results: The subcutaneous chamber containing the islet graft normalized blood glucose in diabetic rodents for up to 3 months.Figure: [Metablic follow up of transplanted rodents]Sufficient graft function depended on oxygen supply. Pre-treatment with GHRH agonist, JI-36, significantly enhanced graft function by improving glucose tolerance and increasing in β-cell insulin reserve thereby allowing for a significant reduction of the islet mass required for metabolic control. As a result of hypervascularization of the tissue surrounding the device, no relevant delay in insulin response to glucose changes has been observed. Despite complete avoidance of immunosuppression in the allogeneic transplantation model, no signs of rejection were observed, indicating a sufficient immunoisolation of the islet graft by the chamber system. Conclusion: A more efficient use of donor islets could facilitate the widespread use of islet transplantation as a treatment approach for type 1 diabetes. We investigated the combination of GHRH agonism with ideal oxygenation using a bioartificial macrochamber. Encapsulated islets are maintained within a device, which creates a sufficient immune barrier and allows for adequate oxygen supply to the islet graft. Together, a new strategy capable of restoring and maintaining long-term euglycemia in diabetic models is thereby presented. Consequently, this system opens up a novel strategy for β-cell replacement therapy without the need for immunosuppression and may even provide a promising avenue for future approaches to xenotransplantation.