Overt Diabetic Research Articles

Positive impact of insulin treatment on clinical trend in cystic fibrosis patients: a retrospective study.

Background Cystic fibrosis related diabetes is a complication of cystic fibrosis (CF). Aim of our study was to evaluate the effects of insulin therapy in overt diabetics or pre-diabetics CF patients on BMI and respiratory function. Methods We selected a sample of 17 insulin treated patients (Group T) and a sample of 17 CF control patients with normal glucose metabolism (Group C). Group T was also subdivided into overt diabetic patients and pre-diabetic patients (IGT, INDET). For treated patients an observation period was established from the first insulin administration to 12 months. For control patients, a comparable year of observation was chosen. Data regarding BMI, FVC, FEV1 and PEF were collected at time 0, and at time 12. The number of hospital admissions for infectious episodes during the year of observation and during the preceding year were recorded for Group T patients. Results The results showed a significant increase in BMI in treated patients compared to control, specially for overt diabetics. The study of spirometric parameters showed a significant improvement of PEF, the main effort-dependent respiratory index, specially for over diabetics, suggesting a hypothetical positive impact of the insulin anabolic action on the magnitude of expiratory effort. In contrast, the study of infectious episodes revealed a significant reduction of hospital admissions in pre diabetic treated patients. Conclusion Overall, our study focuses on the importance of glycemic monitoring during the early stages of CF disease and on the advantage of insulin treatment in the early stages of glucose alteration .

Vertical sleeve gastrectomy triggers fast β-cell recovery upon overt diabetes

ObjectiveThe effectiveness of bariatric surgery in restoring β-cell function has been described in type-2 diabetes (T2D) patients and animal models for years, whereas the mechanistic underpinnings are largely unknown. The possibility of vertical sleeve gastrectomy (VSG) to rescue far-progressed, clinically-relevant T2D and to promote β-cell recovery has not been investigated on a single-cell level. Nevertheless, characterization of the heterogeneity and functional states of β-cells after VSG is a fundamental step to understand mechanisms of glycaemic recovery and to ultimately develop alternative, less-invasive therapies. MethodsWe performed VSG in late-stage diabetic db/db mice and analyzed the islet transcriptome using single-cell RNA sequencing (scRNA-seq). Immunohistochemical analyses and quantification of β-cell area and proliferation complement our findings from scRNA-seq. ResultsWe report that VSG was superior to calorie restriction in late-stage T2D and rapidly restored normoglycaemia in morbidly obese and overt diabetic db/db mice. Single-cell profiling of islets of Langerhans showed that VSG induced distinct, intrinsic changes in the β-cell transcriptome, but not in that of α-, δ-, and PP-cells. VSG triggered fast β-cell redifferentiation and functional improvement within only two weeks of intervention, which is not seen upon calorie restriction. Furthermore, VSG expanded β-cell area by means of redifferentiation and by creating a proliferation competent β-cell state. ConclusionCollectively, our study reveals the superiority of VSG in the remission of far-progressed T2D and presents paths of β-cell regeneration and molecular pathways underlying the glycaemic benefits of VSG.

Histopathological study with immunohistochemical expression of vascular endothelial growth factor in placentas of hyperglycemic and diabetic women.

AIMS AND OBJECTIVES:Spectrum of hyperglycemia in pregnancy includes gestational diabetes mellitus (GDM), mild hyperglycemia, and overt diabetes. Many authors have worked on morphological changes of the placenta in diabetes, but few studies have correlated histopathological changes with vascular endothelial growth factor (VEGF) immunoexpression. The aim of this study was to detect different histopathological changes in various groups of diabetic placentas and to correlate with VEGF immunoexpression.MATERIALS AND METHODS:Pregnant women were screened for diabetes. They were subsequently divided into normoglycemic (12 cases), GDM (33 cases), mild hyperglycemic (13 cases), and overt diabetes (18 cases). Placentas collected were subjected to histopathological examination. VEGF expressions were studied by immunohistochemistry.RESULTS:Overt diabetic placenta displayed villous immaturity (44.4%), villous edema (38.9%), chorangiosis (61.1%), fibrinoid substance deposition (38.9%), and Hofbauer cell hyperplasia in 44.4% cases. GDM placentas displayed villous immaturity (45.5%), villous edema (45.5%), chorangiosis (42.4%), and fibrinoid substance deposition in 75.6% cases. Mild hyperglycemic placentas displayed villous immaturity (38.5%), chorangiosis (61.5%), and fibrinoid substance deposition in 61.5% cases. VEGF immunoexpression in GDM placentas was absent in all placental components except syncytiotrophoblast. VEGF expression in overt diabetic placentas was increased in syncytiotrophoblast and capillary endothelium compared to normoglycemic placentas. Mild hyperglycemic placentas expressed similar VEGF expression in all components when compared to normoglycemic controls. However, it displayed weak expression in vessel endothelium.CONCLUSION:Histopathological changes in diabetic placentas might be a consequence of altered or abnormal VEGF expression in diabetic placentas. Pathogenesis and VEGF expression in GDM placentas are significantly different from overt diabetic placentas.

Insulin sensitizer prevents and ameliorates experimental type 1 diabetes.

Insulin-dependent type-1 diabetes (T1D) is driven by autoimmune β-cell failure, whereas systemic resistance to insulin is considered the hallmark of insulin-independent type-2 diabetes (T2D). In contrast to this canonical dichotomy, insulin resistance appears to precede the overt diabetic stage of T1D and predict its progression, implying that insulin sensitizers may change the course of T1D. However, previous attempts to ameliorate T1D in animal models or patients by insulin sensitizers have largely failed. Sensitization to insulin by MEthyl-substituted long-chain DICArboxylic acid (MEDICA) analogs in T2D animal models surpasses that of current insulin sensitizers, thus prompting our interest in probing MEDICA in the T1D context. MEDICA efficacy in modulating the course of T1D was verified in streptozotocin (STZ) diabetic rats and autoimmune nonobese diabetic (NOD) mice. MEDICA treatment normalizes overt diabetes in STZ diabetic rats when added on to subtherapeutic insulin, and prevents/delays autoimmune T1D in NOD mice. MEDICA treatment does not improve β-cell insulin content or insulitis score, but its efficacy is accounted for by pronounced total body sensitization to insulin. In conclusion, potent insulin sensitizers may counteract genetic predisposition to autoimmune T1D and amplify subtherapeutic insulin into an effective therapeutic measure for the treatment of overt T1D.

Sensory Functions, Balance, and Mobility in Older Adults With Type 2 Diabetes Without Overt Diabetic Peripheral Neuropathy: A Brief Report.

This study examined possible subtle degradation in sensory functions, balance, and mobility in older adults with type 2 diabetes (T2D) prior to overt development of diabetic peripheral neuropathy (DPN). Twenty-five healthy controls (HC group, age = 74.6 ± 5.4) and 35 T2D elderly without DPN (T2D group, age = 70.6 ± 4.7) were recruited. Sensory assessment included vibrotactile sensitivity, bilateral caloric weakness, and visual contrast sensitivity. Self-report measures comprised of Activity-Specific Balance Confidence (ABC), Human Activity Profile-adjusted activity scores (HAP-AAS), falls, and mobility disability. Performance measures included modified Timed-Up and Go (mTUG), Clinical Test of Sensory Integration for Balance (mCTSIB), and Frailty and Injuries (FICSIT-4) balance test. T2D group demonstrated significantly worse bilateral caloric weakness, marginally higher threshold of vibrotactile sensitivity and lower visual contrast sensitivity, and as well as signifcantly lower HAP-AAS. A significantly higher proportion of the T2D group failed mCTSIB Condition 4 than in the HC group. Subtle changes in multiple sensory systems of older adults with T2D may reduce redundancy available for balance control while performing challenging activities much before DPN development.

5. 顕性腎症合併妊婦の管理と対策―母体長期予後を含めたエビデンスに基づくガイドラインの提唱―

5. 顕性腎症合併妊婦の管理と対策―母体長期予後を含めたエビデンスに基づくガイドラインの提唱―

Avosentan for Overt Diabetic Nephropathy

In the short term, the endothelin antagonist avosentan reduces proteinuria, but whether this translates to protection from progressive loss of renal function is unknown. We examined the effects of avosentan on progression of overt diabetic nephropathy in a multicenter, multinational, double-blind, placebo-controlled trial. We randomly assigned 1392 participants with type 2 diabetes to oral avosentan (25 or 50 mg) or placebo in addition to continued angiotensin-converting enzyme inhibition and/or angiotensin receptor blockade. The composite primary outcome was the time to doubling of serum creatinine, ESRD, or death. Secondary outcomes included changes in albumin-to-creatinine ratio (ACR) and cardiovascular outcomes. We terminated the trial prematurely after a median follow-up of 4 months (maximum 16 months) because of an excess of cardiovascular events with avosentan. We did not detect a difference in the frequency of the primary outcome between groups. Avosentan significantly reduced ACR: In patients who were treated with avosentan 25 mg/d, 50 mg/d, and placebo, the median reduction in ACR was 44.3, 49.3, and 9.7%, respectively. Adverse events led to discontinuation of trial medication significantly more often for avosentan than for placebo (19.6 and 18.2 versus 11.5% for placebo), dominated by fluid overload and congestive heart failure; death occurred in 21 (4.6%; P = 0.225), 17 (3.6%; P = 0.194), and 12 (2.6%), respectively. In conclusion, avosentan reduces albuminuria when added to standard treatment in people with type 2 diabetes and overt nephropathy but induces significant fluid overload and congestive heart failure.

Vascular change in the placenta of diabetic mothers and hypertensive diabetic mothers

Pregnancy complicated by diabetes and/or hypertension is a significant medical problem not only affecting maternal health, but also jeopardizing fetal normalcy. The placenta being the bridge between maternal fetal activity, this structure is considered as a window through which understanding of maternal dysfunctions as well as of their impacts on fetal wellbeing can be obtained. And as it is an almost all-vessel organ, its functional status depends primarily on the structural status of its vessels. To observe vascular changes in the placenta, a study was carried out on 44 placentas.19 from overt diabetic mothers having no hypertension and 5 from hypertensive diabetic mothers, and 20 from control group having no hypertension or diabetes. These were collected just after delivery though caesarian section. Macroscopic findings of the study was that there was a trend of increase weight, volume and number of cotyledons in overt diabetes group, where as the in the hypertensive diabetes group was the opposite. But none of these levels has reached a significant level. For all these variables, the hypertensive diabetes group had smaller values than the overt diabetes group, significantly so for the number of cotyledons. The placental diameter was non-significantly larger in the overt diabetes group than in the control group, but a smaller than control value was found in the hypertensive diabetes group. Although neonatal weight did not show any significant change in either group, but in overt diabetes group, it showed a significant positive correlation with placental weight.

OBESITY AND GLUCOSE INTOLERANCE ARE ASSOCIATED WITH DIASTOLIC DYSFUNCTION: EXPOSING THE ACHILLES HEEL OF EARLY DIABETIC CARDIOMYOPATHY.

Background The alarming rise in the incidence of obesity has paralleled the surge in the incidence of impaired glucose tolerance (prediabetes) and overt diabetes. The cardiovascular sequelae of insulin resistance are thought to occur later, along with the development of atherosclerotic coronary artery disease. Yet emerging evidence suggesting early organ dysfunction in insulin resistance (such as nonalcoholic steatohepatitis) points to an early visceral ectopic fat deposition referred to as lipotoxicity. We sought to evaluate the effects of insulin resistance and impaired glucose tolerance on cardiac function in otherwise healthy overweight volunteers. Methods Twenty healthy obese and overweight volunteers (mean age 42 ± 6 years; 15 females) underwent glucose tolerance testing, direct insulin measurements, as well as dual x-ray absorptiometry (DXA, to assess subcutaneous and visceral fat mass). The cardiac evaluation included complete two-dimensional, Doppler, and tissue velocity imaging (TVI). The postprocessing of the TVI data was performed on an EchoPac work station (GE Health Systems) and the data were analyzed using Pearson correlation model and unpaired Student9s t-test. Results The mean weight of the subjects was 90 ± 12 kg, mean BMI of 32 ± 4 kg/m2, and mean systolic BP of 127 ± 15. The mean fasting blood glucose levels was 91 ± 13 with a mean HbA1C of 5.7 ± 0.4. The peak diastolic strain rate showed a significant inverse relationship with subcutaneous fat mass as well as fasting and 2-hour blood glucose levels (r = .54, p Conclusion Diastolic dysfunction occurs early in the course of obesity and glucose intolerance and may be a precursor of overt diabetic cardiomyopathy.

Effect of rosiglitazone on the differential expression of diabetes-associated proteins in pancreatic islets of C57Bl/6 lep/lep mice.

The insulin sensitizer drug, rosiglitazone, has been shown to have a protective effect on pancreatic islet cell structure and function in animal models of type 2 diabetes. The identification of new molecular targets associated both with islet cell dysfunction and protection is a crucial research goal. In the present study, a proteomics approach has been used to identify such targets. Obese C57Bl/6J lep/lep mice and lean littermates were given the insulin sensitizer drug BRL49653, rosiglitazone. It normalized the impaired glucose tolerance in lep/lep mice but had no significant effect on glucose tolerance in the lean mice. Pancreatic islet polypeptides were arrayed by a two-dimensional gel electrophoresis system that separated more than 2500 individual spots. Three overexpressed and six underexpressed proteins were significant (p < 0.05) between lep/lep and lean mice, and four were modulated significantly (p < 0.05) by the rosiglitazone treatment of the obese mice. The identity of these differentially expressed proteins was made using mass spectrometric analysis and provided evidence that differential expression of actin-binding proteins may be an important aspect of defective islet function. Rosiglitazone increased carboxypeptidase B expression in both lep/lep and normal mice suggesting that this might be an independent effect of rosiglitazone that contributes to improved insulin processing.

Profiling of Zucker diabetic fatty rats in their progression to the overt diabetic state

Blood chemistry profiles (glucose, insulin, and triglycerides) and indirect calorimetry were performed on male Zucker diabetic fatty (ZDF) rats in a longitudinal fashion (starting at 7 weeks of age) to assess the nature and timing of specific events in the transition to overt diabetes. Peripheral (skeletal muscle) insulin resistance was clearly present at 7 weeks of age in ZDF rats, yet circulating glucose was only slightly above normal as a result of compensatory hyperinsulinemia. At a crucial stage from 7 to 8 weeks, a reduction in insulin levels instigated several deleterious changes resulting in reduced whole-body carbohydrate utilization and increased glycemia. In subsequent weeks, an inability to sustain peripheral glucose disposal as a consequence of a continuous decline in insulin levels further reduced carbohydrate utilization (increased lipid utilization) and enhanced the overt hyperglycemia. These observations document in a systematic fashion the alterations that define diabetic progression in ZDF rats.

The Role of Dietary Zinc in Modifying the Onset and Severity of Spontaneous Diabetes in the BB Wistar Rat

The goal of this study was to determine whether zinc supplementation in the diet of diabetes-prone BB Wistar rats will delay or prevent the onset of overt diabetes. Male Wistar BB rats were fed diets containing either 1000 ppm (HZ), 50 ppm (NZ), or 1 ppm zinc (LZ) starting at 30 days of age. Non-diabetes-prone rats were fed NZ and designated as controls (NORM). Beginning at 60 days, the rats were checked for glycosuria and, if positive, were given an ip glucose tolerance test (IPGTT). All remaining animals underwent an IPGTT at 100 days and were sacrificed. At 90 days of age HZ rats had a lower incidence of diabetes (19%) than NZ (53%) or LZ (44%) animals (P< 0.015). By age 100 days, for the HZ group, there was a 60% reduction in the number of expected overt diabetic rats. HZ animals also had higher concentrations of both pancreatic and serum insulin and exhibited lower serum glucose and triglycerides. Immunohistochemistry of HZ rats was clearly different from NZ rats and showed evidence of nearly normal pancreatic endocrine activity. Data indicate that dietary treatment of diabetes-prone BB Wistar rats with zinc appears to be an effective approach for delaying or preventing the onset of diabetes in genetically predisposed rodents. This finding may suggest further experimental studies regarding dietary means for preservation of pancreatic function.

Pathomorphologic aspects of muscular tissue in diabetes mellitus

Biopsy specimens from the myocardium were examined in a series of 145 patients who had elected coronary arterial bypass grafting. The patients were divided into three groups; 1) overtly diabetic (OD) patients; 2) chemically diabetic (CD) patients, who demonstrated impaired glucose tolerance only when stressed with a sugar load; and 3) normoglycemic, nondiabetic (ND) patients, who served as a control group. Tissue plugs from the left anterior apical segment of the heart and from the quadriceps femoris in 71 patients, for comparative evaluation, were prepared for ultrastructural examination. Findings were as follows: 1) Myocardial hypertrophy and interstitial fibrosis were twin characteristic abnormalities, seen in all but two of the biopsy specimens; capillary endothelial changes, the third most common abnormality, were present in approximately half of these specimens, regardless of the patients' metabolic status. 2) In patients matched by sex, age, weight, blood pressure, preoperative myocardial ventricular function, and coronary arterial integrity, capillary basal laminar thickening represented a pathomorphologic hallmark, distinguishing structural alterations in the diabetic from those in the normoglycemic patient. 3) Although clear-cut and statistically significant thickening of basal laminae was noticeable in OD patients, a) in the quadriceps markedly increased laminar thickening was present in a number of ND patients, rendering interpretation of this change in skeletal muscle as pathognomonic for diabetes doubtful; and b) within cardiac muscle this increase in laminar width was less than that seen in skeletal muscle, leaving the functional implications of this alteration in doubt. 4) Early but statistically significant increases in capillary basal laminar thickening were observed in the myocardium of CD patients; these patients demonstrated impaired glucose tolerance only when stressed with a sugar load, without exhibiting overt diabetic manifestations. 5) In this group of highly selected patients with epicardial coronary arterial disease, the histopathologic profile of the diabetic myocardium did not include distinctive abnormalities sufficient to warrant the designation of "diabetic cardiomyopathy," indicating that coronary arterial bypass grafting can be recommended for the diabetic patient who requires this procedure.

Correlations between plasma insulin and body weight in obesity, anorexia nervosa and diabetes mellitus.

Determinations of plasma insulin levels (IRI) were performed in 79 patients before and after a quick intravenous glucose load (0.33 g/kg body weight). The patients were divided in normals (N), underweight patients (M), obese (O), latent diabetics (D1) and overt diabetics (D2), obese latent diabetics (OD1) and obese diabetics (OD2). The body weight varied from 59 to 290 per cent of ideal body weight and the age from 14 to 75 years. We were unable to find any significant correlation between basal IRI values and body weight. We found significant correlations between IRI values obtained after glucose administration and body weight. The insulinogenic index rises with increasing body weight in all subjects, in non diabetics (N-M-O) as well as in diabetics (D1-D2-OD1-OD2). In undernutrition due to anorexia nervosa, the basal plasma IRI and the plasma IRI increase after the glucose load are normal in the studied patients. Overt diabetic patients (D2 and OD2) were significantly older than non diabetic patients having the same body weight (N-O). The insulinogenic index fell with increasing age in obese and in diabetic patients. The correlations between plasma IRI and blood sugar are discussed.

Micro Vascular Changes in the Placenta of Bangladeshi Overt Diabetic Mothers and Hypertensive Diabetic Mothers

It is a significant medical problem when Pregnancy is complicated by diabetes and/or hypertension which affect not only affecting maternal health, but also jeopardizing fetal normalcy? The placenta being the bridge between maternal fetal activities, this structure is considered as a window through which understanding of maternal dysfunctions as well as of their impacts on fetal wellbeing can be obtained. And as it is an almost all-vessel organ, its functional status depends primarily on the structural status of its vessels. To observe vascular changes in the placenta, a study was carried out on 44 placentas.19 from overt diabetic mothers having no hypertension and 5 from hypertensive diabetic mothers, and 20 from control group having no hypertension or diabetes. These were collected just after delivery though caesarian section. Microscopic findings of the study were that there was a trend of greater intimal thickness at the second branching site in the overt diabetes group than the control group. But at the first and last branching site this tendency was reversed. But none of these tendencies reached statistical significance. In case of the hypertensive diabetes group, there was a tendency of greater intimal thickness at the first, second and last branching sites as compared to the control group. Hypertensive diabetes group also showed significantly greater intimal thickness at first and last branching sites than the overt diabetes group. &#x0D; &#x0D; Key words: Placenta, diabetes, blood vessels, hypertension&#x0D; &#x0D; J Bangladesh Soc Physiol. 2006 Dec;(1):27-34