Non-fasting Plasma Glucose Research Articles

Prevalence of type 2 diabetes and prediabetes in the Faroe Islands

AimsTo determine the prevalence of type 2 diabetes mellitus and prediabetes among the population aged 40–74 years in the Faroe Islands. MethodsThis population-based cross-sectional survey, conducted between 2011 and 2012, invited 2186 randomly selected individuals (corresponding to 11.1% of the entire population aged 40–74 years). Subjects were screened using finger capillary blood for glycosylated hemoglobin, type A1c, non-fasting random plasma glucose, fasting plasma glucose followed by oral glucose tolerance test. The test was based on an algorithm that accounts for screening, diagnostic and confirmatory steps. Anthropometric measures and a questionnaire including medical history, medication, hereditary conditions, and food intake were included. ResultsThe study included 1772 participants. Of the 1772, 169 (9.5%) had type 2 diabetes mellitus (3.0% of which were diagnosed upon study inclusion), thus 31.4% of subjects with diabetes were undiagnosed at the time of examination. A total of 271 (15.3%) had prediabetes. Diabetes was more prevalent among men, significantly from age ≥60 years. Women had lower mean fasting plasma glucose concentrations and men had lower values for 2-h plasma glucose. Predictors associated with diabetes mellitus included obesity (BMI ≥ 30), abnormal waist/hip ratio, history of hypertension or cardiovascular attack and family history of diabetes mellitus and leisure activity. ConclusionsThe prevalences of diabetes and prediabetes increased with age and were more frequent among men. The detected prevalence in the Faroe Islands was slightly higher than other Nordic countries.

Ethnic Differences in the Prevalence and Risk Factors of Diabetic Retinopathy: The Singapore Epidemiology of Eye Diseases Study

To evaluate the prevalence and risk factors for diabetic retinopathy (DR) in the Singapore Epidemiology of Eye Diseases (SEED) Study. Population-based, cross-sectional study. Persons of Malay, Indian, and Chinese ethnicity aged 40+ years, living in Singapore. Diabetes was defined as nonfasting plasma glucose ≥200 mg/dl (11.1 mmol/l), glycated hemoglobin A1c (HbA1c) >6.5%, self-reported physician-diagnosed diabetes, or the use of glucose-lowering medication. Retinal photographs, were graded for the presence and severity of DR using the modified Airlie House classification system. Diabetic retinopathy, diabetic macular edema (DME), vision-threatening diabetic retinopathy (VTDR), defined as the presence of severe nonproliferative or proliferative DR, or clinically significant macular edema (CSME). Of the 10 033 subjects, 2877 (28.7%) had diabetes and gradable photographs for analysis. The overall age-standardized prevalence (95% confidence interval [CI]) was 28.2% (25.9-30.6) for any DR, 7.6% (6.5-9.0) for DME, and 7.7% (6.6-9.0) for VTDR. Indians had a higher prevalence of any DR (30.7% vs. 26.2% in Chinese and 25.5% in Malays, P= 0.012); a similar trend was noted for any DME (P= 0.001) and CSME (P= 0.032). Independent risk factors for any DR were Indian ethnicity (odds ratio [OR], 1.41; 95% CI, 1.09-1.83, vs. Chinese), diabetes duration (OR, 1.10; 95% CI, 1.08-1.11, per year), HbA1c (OR, 1.25; 95% CI, 1.18-1.32, per %), serum glucose (OR, 1.03; 95% CI, 1.00-1.06, per mmol/l), and systolic blood pressure (OR, 1.14; 95% CI, 1.09-1.19, per 10 mmHg). Diastolic blood pressure (OR, 0.74; 95% CI, 0.65-0.84, per 10 mmHg increase), total cholesterol (OR, 0.87; 95% CI, 0.80-0.95, per mmol/l increase), and low-density lipoprotein (LDL) cholesterol (OR, 0.83; 95% CI, 0.74-0.92, per mmol/l increase) were associated with lower odds of any DR. Risk factors were largely similar across the 3 ethnic groups. Indian Singaporeans have a higher prevalence of DR and DME compared with Chinese and Malays. Major risk factors for DR in this study were similar across the 3 ethnic groups. Addressing these risk factors may reduce the impact of DR in Asia, regardless of ethnicity.

Skin autofluorescence improves the Finnish Diabetes Risk Score in the detection of diabetes in a large population-based cohort: The LifeLines Cohort Study

AimThe aim of the present study was to investigate whether skin autofluorescence would improve the Finnish Diabetes Risk Score (FINDRISC) in detecting undiagnosed diabetes in a large population-based cohort. MethodsIncluded were participants from the Dutch LifeLines Cohort Study. Skin autofluorescence was assessed in an unselected subset of participants using the AGE Reader. After the exclusion of participants with previously diagnosed diabetes (n=1635), pregnant women (n=58) and those using corticosteroids (n=345), 79,248 subjects were eligible for analysis. Diabetes was defined as fasting plasma glucose ≥7.0mmol/L, non-fasting plasma glucose ≥11.1mmol/L or HbA1c ≥6.5% (48mmol/mol). ResultsDiabetes was detected in 1042 participants (aged 55±12 years; 54% male). Skin autofluorescence improved the area under the receiver operating characteristic (AUROC) curve of the FINDRISC model from 0.802 to 0.811 (P<0.001). Furthermore, the addition of skin autofluorescence to FINDRISC reclassified 8–15% of all participants into more accurate risk categories (NRI: 0.080, 95% CI: 0.052–0.110). The proportion of reclassified participants was especially high (>30%) in the intermediate (1% to <5% and 5% to<10%) risk categories. When skin autofluorescence was added to a simplified model (age+body mass index), its discriminatory performance was similar to the full model+skin autofluorescence (AUROC: 0.806, P=0.062). ConclusionSkin autofluorescence is a non-invasive tool that can be used to further improve the FINDRISC for diabetes detection. The new resultant model is especially useful for reclassifying people in the intermediate-risk categories, where additional blood glucose testing is needed to confirm the presence of diabetes.

Molecular mechanisms mediating the beneficial metabolic effects of [Arg4]tigerinin-1R in mice with diet-induced obesity and insulin resistance

The frog skin host-defense peptide tigerinin-1R stimulates insulin release in vitro and improves glucose tolerance and insulin sensitivity in animal models of type 2 diabetes. This study extends these observations by investigating the molecular mechanisms of action underlying the beneficial metabolic effects of the analogue [Arg4]tigerinin-1R in mice with diet-induced obesity, glucose intolerance and insulin resistance. The study also investigates the electrophysiological effects of the peptide on KATP and L-type Ca2+ channels in BRIN-BD11 clonal β cells. Non-fasting plasma glucose and glucagon concentrations were significantly (p<0.05) decreased and plasma insulin increased by twice daily treatment with [Arg4]tigerinin-1R (75 nmol/kg body weight) for 28 days. Oral and intraperitoneal glucose tolerance were significantly (p<0.05) improved accompanied by enhanced secretion and action of insulin. The peptide blocked KATP channels and, consistent with this, improved beta cell responses of isolated islets to a range of secretagogues. Peptide administration resulted in up-regulation of key functional genes in islets involved insulin secretion (Abcc8, Kcnj11, Cacna1c and Slc2a2) and in skeletal muscle involved with insulin action (Insr, Irs1, Pdk1, Pik3ca, and Slc2a4). These observations encourage further development of tigerinin-1R analogues for the treatment of patients with type 2 diabetes.

Longitudinal association between toenail zinc levels and the incidence of diabetes among American young adults: The CARDIA Trace Element Study.

Data on primary prevention of zinc status and diabetes risk are sparse and inconsistent. Of note, the previous studies measured either dietary zinc intake with questionnaire or zinc status in serum or hair. Toenail zinc levels are reliable biomarkers of a relatively long-term exposure. A total of 3,960 American young adults, aged 20–32 years, free of diabetes at baseline in 1987 when toenail clippings were collected, were examined for incident diabetes through 2010. Toenail zinc levels were measured with an inductively-coupled-plasma mass spectroscopy method. Incident diabetes cases were identified by fasting or non-fasting plasma glucose levels, oral glucose tolerance tests, hemoglobin A1C levels, and/or antidiabetic medications. During the 23-year follow-up, 418 incident diabetes occurred. After adjusted for age, sex, ethnicity, study center, body mass index, education, smoking status, alcohol consumption, physical activity, family history of diabetes, homeostasis model assessment of insulin resistance, and other dietary and non-dietary potential confounders, the hazard ratio of incident diabetes comparing the highest to the lowest quartile of toenail zinc levels was 1.21 (95% CI: 0.90–1.63; Ptrend = 0.20). Findings from this study do not support the hypothesis that zinc status is inversely and longitudinally associated with the incidence of diabetes in American young adults.

Effect of ipragliflozin, an SGLT2 inhibitor, on progression of diabetic microvascular complications in spontaneously diabetic Torii fatty rats

AimsWe investigated the effect of the selective sodium-dependent glucose cotransporter 2 inhibitor ipragliflozin on the simultaneous progression of diabetic microvascular complications of retinopathy, nephropathy and neuropathy in individual Spontaneously Diabetic Torii (SDT) fatty rats. Main methodsIpragliflozin was administered to male SDT fatty rats for 12weeks. Male Sprague–Dawley rats of the same age were used as non-diabetic controls. Non-fasting plasma glucose and glycated hemoglobin levels were measured every 4weeks. Cataract formation was monitored once a week, and the electroretinogram was measured after 6weeks of treatment. After the treatment period, motor nerve conduction velocity was measured and urinalysis was conducted. Tissue samples were then dissected for histopathological examination. Key findingsTreatment with ipragliflozin reduced glycated hemoglobin levels, inhibited the progression of cataract formation, prevented the prolongation of oscillatory potential peaks in the electroretinogram, ameliorated the slowing of motor nerve conduction velocity, and reduced the severity of glomerulosclerosis in SDT fatty rats. SignificanceThese results suggest that the control of hyperglycemia with ipragliflozin slows the progression of the diabetic complications of retinopathy, nephropathy, and neuropathy.

Esculentin-2CHa-Related Peptides Modulate Islet Cell Function and Improve Glucose Tolerance in Mice with Diet-Induced Obesity and Insulin Resistance.

The frog skin host-defense peptide esculentin-2CHa (GFSSIFRGVA10KFASKGLGK D20LAKLGVDLVA30CKISKQC) displays antimicrobial, antitumor, and immunomodulatory properties. This study investigated the antidiabetic actions of the peptide and selected analogues. Esculentin-2CHa stimulated insulin secretion from rat BRIN-BD11 clonal pancreatic β-cells at concentrations greater than 0.3 nM without cytotoxicity by a mechanism involving membrane depolarization and increase of intracellular Ca2+. Insulinotropic activity was attenuated by activation of KATP channels, inhibition of voltage-dependent Ca2+ channels and chelation of extracellular Ca2+. The [L21K], [L24K], [D20K, D27K] and [C31S,C37S] analogues were more potent but less effective than esculentin-2CHa whereas the [L28K] and [C31K] analogues were both more potent and produced a significantly (P < 0.001) greater maximum response. Acute administration of [L28K]esculentin-2CHa (75 nmol/kg body weight) to high fat fed mice with obesity and insulin resistance enhanced glucose tolerance and insulin secretion. Twice-daily administration of this dose of [L28K]esculentin-2CHa for 28 days had no significant effect on body weight, food intake, indirect calorimetry or body composition. However, mice exhibited decreased non-fasting plasma glucose (P < 0.05), increased non-fasting plasma insulin (P < 0.05) as well as improved glucose tolerance and insulin secretion (P < 0.01) following both oral and intraperitoneal glucose loads. Impaired responses of isolated islets from high fat fed mice to established insulin secretagogues were restored by [L28K]esculentin-2CHa treatment. Peptide treatment was accompanied by significantly lower plasma and pancreatic glucagon levels and normalization of α-cell mass. Circulating triglyceride concentrations were decreased but plasma cholesterol and LDL concentrations were not significantly affected. The data encourage further investigation of the potential of esculentin-2CHa related peptides for treatment of patients with type 2 diabetes.

Effects of E2HSA, a Long-Acting Glucagon Like Peptide-1 Receptor Agonist, on Glycemic Control and Beta Cell Function in Spontaneous Diabetic db/db Mice.

Glucagon like peptide-1 (GLP-1) receptor agonists such as exendin-4 have been widely used but their short half-life limits their therapeutic value. The recombinant protein, E2HSA, is a novel, long-acting GLP-1 receptor agonist generated by the fusion of exendin-4 with human serum albumin. In mouse pancreatic NIT-1 cells, E2HSA activated GLP-1 receptor with similar efficacy as exendin-4. After single-dose administration in ICR mice, E2HSA showed prolonged glucose lowering effects which lasted up to four days and extended inhibition on gastric emptying for at least 72 hours. Chronic E2HSA treatment in db/db mice significantly improved glucose tolerance, reduced elevated nonfasting and fasting plasma glucose levels, and also decreased HbA1c levels. E2HSA also increased insulin secretion and decreased body weight and appetite. Furthermore, immunofluorescence analysis showed that E2HSA increased β-cell area, improved islet morphology, and reduced β-cell apoptosis. In accordance with the promotion of β-cell function and survival, E2HSA upregulated genes such as Irs2, Pdx-1, Nkx6.1, and MafA and downregulated the expression levels of FoxO1 and proapoptotic Bcl-2 family proteins. In conclusion, with prolonged glucose lowering effects and promoting β-cell function and survival, the fusion protein, E2HSA, is a promising new therapeutic for once weekly treatment of type 2 diabetes.

Follow-up of patients with hyperglycemia in the emergency department without a history of diabetes mellitus

ObjectivesThe aim of this study is to determine the prevalence of hyperglycemia in emergency department patients without a history of diabetes mellitus, and to investigate whether these patients were referred to a general practitioner or to the outpatient clinic for follow-up with further diagnostic testing and treatment. MethodsWe conducted a retrospective cohort pilot study of adult patients who were seen at the emergency department of an urban academic hospital in the Netherlands between the 1st of January and the 29th of February 2008, who had an initial (unknown fasting or non-fasting) plasma glucose level ≥7.8mmol/L (140mg/dL). The medical records of these patients were retrieved to evaluate whether these patients were referred for follow-up. ResultsDuring the data collecting period 5317 patients presented at the ED, 343 of these patients were identified with a plasma glucose ≥7.8mmol/L. Using exclusion criteria, eventually 154 patients were included in this study. The prevalence of incidentally found hyperglycemia in emergency department patients without a history of diabetes mellitus in this period was 2.9%.For 98.7% of the hyperglycemic patients no follow-up was arranged by the treating physician. None of the patients was treated with a hypoglycemic agent in the emergency department. ConclusionA substantial percentage (2.9%) of our study population had hyperglycemia and thus was at risk for undiagnosed diabetes mellitus and prediabetes. To date, recognition and follow-up of hyperglycemia in emergency department patients is poor. We presume that major health benefits may be achieved when the follow-up of hyperglycemia is performed more frequently.

Early occurrence of new-onset diabetes after transplantation is related to type of liver graft and warm ischaemic injury.

We studied new-onset diabetes after transplantation (NODAT) in liver transplantation with grafts donated after brain death (DBD) or circulatory death (DCD), focusing on the early post-transplant period. A total of 430 non-diabetic primary liver transplant recipients [DCD, n = 90 (21%)] were followed up for 30 months (range 5-69). NODAT was defined as the composite endpoint of one of following: (i) Two non-fasting plasma glucose levels > 11.1 mmol/L ≥ 30 days apart, (ii) oral hypoglycaemic drugs ≥ 30 days consecutively (iii) insulin therapy ≥ 30 days and (iv) HbA1c ≥ 48 mmol/L. Resolution of NODAT was defined as cessation of treatment or hyperglycaemia. Total of 81/430 (19%) patients developed NODAT. Incidence and resolution of NODAT over time showed significantly different patterns between DCD and DBD liver graft recipients; early occurrence, high peak incidence and early resolution were seen in DCD. In multivariate logistic regression including age, ethnicity, HCV, tacrolimus level and pulsed steroids, only DCD was independently associated with NODAT at day 15 post-transplant (OR 6.5, 95% CI 2.3-18.4, P < 0.001), whereas age and pulsed steroids were significant factors between 30-90 days. Combined in multivariate Cox regression model for NODAT-free survival, graft type, age and pulsed steroids were each independent predictor for decreased NODAT-free survival in the first 90-postoperative days. Early peak of NODAT in DCD graft recipients is a novel finding, occurring independently from known risk factors. Donor warm ischaemia and impact on insulin sensitivity should be further studied and could perhaps be associated with graft function.

Xenograft of Microencapsulated Sertoli Cells for the Cell Therapy of Type 2 Diabetes Mellitus in Spontaneously Diabetic Nonhuman Primates: Preliminary Data

Insulin resistance in type 2 diabetes mellitus (T2DM) may be due to a chronic inflammation of the visceral adipose tissue (VAT) leading to local and systemic increases in proinflammatory cytokines. Microencapsulated porcine Sertoli cells (MC-pSC), by provision of immunomodulatory and trophic factors, have been successfully used to reduce such inflammation in rodent animal models of type 1 diabetes with no complications or deleterious side effects. Herein, we have begun to investigate this novel and safe therapeutic approach in the spontaneously obese nonhuman primate with spontaneous, insulin-dependent T2DM. After MC-pSC intraperitoneal injection we have evaluated, throughout a 6-month follow-up period, daily ad libitum fed glucose levels, daily exogenous insulin supplementation, biweekly body weight measurements, periodic fasting blood glucose concentrations, glycated hemoglobin (HbA1c) levels, glucose tolerance tests (GTT), and fluorescence-activated cell sorting cytometry (FACS) assessment of peripheral blood mononuclear cells. Very preliminarily, we have observed a slight reduction in fasting (FPG) and mean nonfasting (NF) plasma glucose levels. We found minimal changes, only in 1 animal, in daily exogenous insulin requirements and HbA1c levels. Flow cytometric analysis was associated with decrease in CD8+ cells only in 1 recipient with a reduction in mean regulatory T Cells (Treg), whereas interestingly, decrease of B lymphocytes was observed in both animals. These results may suggest that this novel MC-SC–based transplantation protocol might possibly impact the metabolic status of T2DM in higher mammals that are close to humans.

Early Occurrence of New-Onset Diabetes After Transplant Is Related to the Type of Liver Graft and Warm Ischaemic Injury.

New-onset diabetes after transplantation(NODAT) occurs in 25-40% of liver transplant(LT) recipients. Cold ischemia and other etiologies have been attributed; however its association with grafts exposed to warm ischemia(WI) has not been documented. We studied NODAT in LT recipients including grafts donated after circulatory death(DCD). 430 non-diabetic primary LT recipients [DCD,n=90(21%)] were followed up for 929(142-2058) days. NODAT was defined as the composite endpoint of one of following 1. Two non-fasting plasma glucose levels>11.1mmol/L ≥30 days apart, 2. oral hypoglycemics ≥30 days consecutively 3. insulin therapy ≥30 days and 4. HbA1c ≥48 mmol/l. Resolution of NODAT was defined as cessation of treatment/hyperglycemia. Temporal association of NODAT with patient and graft characteristics was analysed. Cumulatively 81/430(19%) developed NODAT after median of 152 days. NODAT was associated with HCV infection (29% vs. 18%;p=0.03), but not with age, sex, ethnicity and BMI. DCD recipients developed NODAT earlier in the postoperative course than DBD grafts (15 vs.32 days;p=0.037) with cumulative peak incidence at 60-90 days of 20% vs. 12% (p 0.048)(Fig 1). Early NODAT(within 30 days) was associated with shorter overall survival in DCD recipients(Log rank test p=0.02;n=90 at risk, n=7 events). Early NODAT in DCD graft recipients is a novel finding in this study. Donor WI and the impact on insulin sensitivity should be further studied and this could perhaps be associated with graft function.Figure 1.: Temporal distribution of occurrence and resolution of NODAT at 15-365 days post-transplant in DBD and DCD graft recipients (Fisher’s exact/Chi2/Linear-by-Linear Association, as appropriate. P-value < 0.05= significant)

Improved glucose tolerance with restored expression of glucose transporter 4 in C57BL/6 mice after a long period of high-fat diet feeding

This study examined the effects of long-term consumption of a high-fat diet (HFD) on glucose metabolism in C57BL/6 mice. A total of 95 male 6-week-old mice were divided into normal diet (ND) and HFD groups until 16, 26, 36, 47, or 77 weeks of age. Plasma and blood glucose and insulin levels and area under the glucose curve (AUCglucose) during an intraperitoneal glucose tolerance test were measured. Quantitative real-time PCR was performed to determine the mRNA expression levels of glucose transporter 4 (GLUT4) in adipose tissue. AUCglucose levels in HFD mice at 16, 26, and 36 weeks were significantly higher than those in ND mice (p < 0.001) and significantly reduced in HFD mice at 47 and 77 weeks. Nonfasting plasma glucose concentrations in both groups were significantly decreased at 47 and 77 weeks (p ≤ 0.05). Insulin levels in HFD mice at 47 and 77 weeks were 12.5% lower than those at 36 weeks. Relative GLUT4 mRNA expression in adipose tissue of HFD mice was significantly decreased at 26 and 36 weeks and increased at 47 and 77 weeks. These data suggest that the glucose tolerance was impaired by relatively short-term high-fat feeding and significantly improved by very long periods of high-fat feeding with restored GLUT4 expression in adipose tissue in HFD mice. The differential effects of short- and long-term HFD on glucose metabolism must be considered for recharacterizing the diet-induced obesity and clarify the pathogenesis of metabolic disorders in this animal model.

Pleiotropic effects of HNF1A rs1183910 in a population-based study of 60,283 individuals

According to genome-wide association studies (GWAS) a locus in the HNF1A gene has pleiotropic effects on several metabolic traits. In a large single-centre study we used the intronic variant rs1183910 located in a region with no or low recombination rate as an instrument for the HNF1A locus to evaluate pleiotropic effects of this locus on the risk of developing type 2 diabetes, as well as on body composition and levels of non-fasting glucose, lipids, acute-phase reactants, and biomarkers of liver and pancreas function. We investigated 60,283 individuals from the Danish general population who were all examined in the same laboratory, comprising the Copenhagen General Population Study. We confirm previous GWAS findings, namely that the minor rs1183910 A allele is associated with an increased risk of developing type 2 diabetes (p(trend) = 0.003), decreased levels of C-reactive protein (CRP; p(trend) = 6 × 10(-76)) and γ-glutamyltransferase (p(trend) = 4 × 10(-48)), and increased levels of total cholesterol (p(trend) = 3 × 10(-10)) and LDL-cholesterol (p(trend) = 3 × 10(-11)). For the first time, we report that the minor rs1183910 A allele is associated with increased levels of non-fasting plasma glucose (p(trend) = 3 × 10(-5)), apolipoprotein B (ApoB; p(trend) = 1 × 10(-4)) and alkaline phosphatase (p(trend) = 5 × 10(-14)), and decreased levels of bilirubin (p trend = 3 × 10(-5)). Our results suggest that the association with increased risk of type 2 diabetes is driven by high non-fasting glucose levels. The minor rs1183910 A allele prompts a potential adverse metabolic profile with increased levels of non-fasting glucose, total cholesterol, LDL-cholesterol, ApoB, and alkaline phosphatase, but simultaneously has potential beneficial effects through decreased levels of CRP, γ-glutamyltransferase and bilirubin.

Correlation of salivary glucose, blood glucose and oral candidal carriage in the saliva of type 2 diabetics: A case-control study.

Objectives:To study the correlation between blood glucose levels and salivary glucose levels in type 2 diabetic patients, to study the relationship between salivary glucose levels and oral candidal carriage in type 2 diabetic patients and to determine whether salivary glucose levels could be used as a noninvasive tool for the measurement of glycemic control in type 2 diabetics.Study Design:The study population consisted of three groups: Group 1 consisted of 30 controlled diabetics and Group 2 consisted of 30 uncontrolled diabetics based on their random nonfasting plasma glucose levels. Group 3 consisted of 30 healthy controls. Two milliliters of peripheral blood was collected for the estimation of random nonfasting plasma glucose levels and glycosylated hemoglobin (HbA1c). Unstimulated saliva was collected for the estimation of salivary glucose. Saliva was collected by the oral rinse technique for the estimation of candidal counts.Results:The salivary glucose levels were significantly higher in controlled and uncontrolled diabetics when compared with controls. The salivary candidal carriage was also significantly higher in uncontrolled diabetics when compared with controlled diabetics and nondiabetic controls. The salivary glucose levels showed a significant correlation with blood glucose levels, suggesting that salivary glucose levels can be used as a monitoring tool for predicting glycemic control in diabetic patients.Conclusion:The present study found that estimation of salivary glucose levels can be used as a noninvasive, painless technique for the measurement of diabetic status of a patient in a dental set up. Increased salivary glucose levels leads to increased oral candidal carriage; therefore, oral diagnosticians are advised to screen the diabetic patients for any oral fungal infections and further management.

Periodontal health in type 2 diabetics

Background: Periodontitis has been reported as the sixth complication of diabetes in addition to other microvascular and macrovascular complications. Prevention and management of periodontitis is an important component in the management of diabetes mellitus (DM) and physicians treating patients with DM should be alert to recognize the signs of severe periodontitis and refer patients for appropriate management. The aim of this study was to estimate and to compare the periodontal status in diabetics and non-diabetics. Materials and Methods: A total of 150 adults, 100 with type 2 diabetes and 50 without diabetes (control subjects), aged 40-60 years, participated in the study. Diabetic status was determined by estimation of random non-fasting plasma glucose levels and glycosylated hemoglobin levels. Periodontal health was assessed by simplified-oral hygiene index (OHI-S), Loe and Silness gingival index (GI) and community periodontal index (CPI). The data were analyzed using Chi-square, Fisher exact test, analysis of variance and Kruskal-Wallis test. Results: The mean GI, mean OHI and mean CPI score were significantly higher in diabetics than non-diabetics. However, mean OHI was similar in controlled diabetics and non-diabetics. Mean CPI score was significantly increased in controlled diabetics compared to uncontrolled diabetics. Conclusion: Gingivitis, poor oral hygiene and periodontitis were more prevalent in diabetics compared to non-diabetics. Presence of poor periodontal health in diabetics, in spite of similar oral hygiene measures suggest the possibility of altered host response in periodontal tissues in these patients.

A Novel Glucagon-like Peptide-1 (GLP-1)/Glucagon Hybrid Peptide with Triple-acting Agonist Activity at Glucose-dependent Insulinotropic Polypeptide, GLP-1, and Glucagon Receptors and Therapeutic Potential in High Fat-fed Mice

Glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon bind to related members of the same receptor superfamily and exert important effects on glucose homeostasis, insulin secretion, and energy regulation. The present study assessed the biological actions and therapeutic utility of novel GIP/glucagon/GLP-1 hybrid peptides. Nine novel peptides were synthesized and exhibited complete DPP-IV resistance and enhanced in vitro insulin secretion. The most promising peptide, [dA(2)]GLP-1/GcG, stimulated cAMP production in GIP, GLP-1, and glucagon receptor-transfected cells. Acute administration of [dA(2)]GLP-1/GcG in combination with glucose significantly lowered plasma glucose and increased plasma insulin in normal and obese diabetic (ob/ob) mice. Furthermore, [dA(2)]GLP-1/GcG elicited a protracted glucose-lowering and insulinotropic effect in high fat-fed mice. Twice daily administration of [dA(2)]GLP-1/GcG for 21 days decreased body weight and nonfasting plasma glucose and increased circulating plasma insulin concentrations in high fat-fed mice. Furthermore, [dA(2)]GLP-1/GcG significantly improved glucose tolerance and insulin sensitivity by day 21. Interestingly, locomotor activity was increased in [dA(2)]GLP-1/GcG mice, without appreciable changes in aspects of metabolic rate. Studies in knock-out mice confirmed the biological action of [dA(2)]GLP-1/GcG via multiple targets including GIP, GLP-1, and glucagon receptors. The data suggest significant promise for novel triple-acting hybrid peptides as therapeutic options for obesity and diabetes.

Alterations of Glucose-Dependent Insulinotropic Polypeptide and Expression of Genes Involved in Mammary Gland and Adipose Tissue Lipid Metabolism during Pregnancy and Lactation

Gastric inhibitory polypeptide (GIP) is a gut derived peptide with multiple emerging physiological actions. Effects of pregnancy and lactation on GIP secretion and related gene expression were studied in Wistar rats. Pregnancy moderately increased feeding (p<0.05), whilst lactation substantially increased food intake (p<0.01 to p<0.001). Circulating GIP was unchanged during pregnancy, but non-fasting plasma glucose was significantly (p<0.01) decreased and insulin increased (p<0.05). Lactation was associated with elevated circulating GIP concentrations (p<0.001) without change of glucose or insulin. Oral glucose resulted in a significantly (p<0.001) decreased glycaemic excursion despite similar glucose-induced GIP and insulin concentrations in lactating rats. Pregnant rats had a similar glycaemic excursion but exhibited significantly lowered (p<0.05) GIP accompanied by elevated (p<0.001) insulin levels. Pregnant rats exhibited increased (p<0.001) islet numbers and individual islet areas were enlarged (p<0.05). There were no significant differences in islet alpha-cell areas, but all groups of rats displayed co-expression of glucagon and GIP in alpha-cells. Lactating rats exhibited significantly (p<0.01) increased intestinal weight, whereas intestinal GIP stores were significantly (p<0.01) elevated only in pregnant rats. Gene expression studies in lactating rats revealed prominent (p<0.01 to p<0.001) increases in mammary gland expression of genes involved in energy turnover, including GIP-R. GIP was present in intestines and plasma of 17 day old foetal rats, with substantially raised circulating concentrations in neonates throughout the period of lactation/suckling. These data indicate that changes in the secretion and action of GIP play an important role in metabolic adaptations during pregnancy and especially lactation.

Effects of short-term chemical ablation of glucagon signalling by peptide-based glucagon receptor antagonists on insulin secretion and glucose homeostasis in mice

Glucagon is a hormone with important effects on blood glucose regulation. This study has utilized the stable glucagon receptor antagonists, desHis¹Pro⁴Glu⁹-glucagon and desHis¹Pro⁴Glu⁹(Lys¹²PAL)-glucagon, to evaluate the effects of sustained inhibition of glucagon receptor signalling in normal mice. Twice-daily injection of either analogue for 10 days had no effect on food intake, body weight and non-fasting plasma glucose concentrations. However, insulin levels were significantly raised (p<0.05 to p<0.01) from day 3 onwards in desHis¹Pro⁴Glu⁹-glucagon mice. After 10 days, glucose tolerance was improved (p<0.05) in desHis¹Pro⁴Glu⁹-glucagon treated mice. Glucose-mediated insulin secretion and circulating cholesterol levels were significantly (p<0.05 to p<0.01) decreased in both treatment groups. Importantly, the effects of glucagon to increase blood glucose and insulin concentrations were still annulled on day 10. Insulin sensitivity was almost identical in all groups of mice at the end of the study. In addition, no changes in pancreatic insulin and glucagon content or islet morphology were observed in either treatment group. Finally, acute injection of desHis¹Pro⁴Glu⁹-glucagon followed by a 24-h fast in treatment naïve mice was not associated with any hypoglycaemic episodes. These data indicate that peptide-based glucagon receptor antagonists represent safe and effective treatment options for type 2 diabetes.

Variability between self-reported diabetes and measured glucose among health screening participants in South Central Kentucky

AimsTo assess self-reported diabetes and random glucose among health screening participants and examine factors associated with these two diabetes outcomes. MethodsStudy subjects were adults aged ≥18 years who participated in diabetes screenings via a mobile health clinic operated by the Institute for Rural Health at Western Kentucky University from 2006 to 2011. Data on self-reported diabetes were based on physicians’ past diagnosis. Random plasma glucose was obtained during the screenings. Non-fasting plasma glucose levels of ≥180mg/dl and ≥140mg/dl were used as cutoffs to determine diabetes and diabetes or pre-diabetes, respectively. Logistic regression was used to examine factors associated with self-reported diabetes and elevated non-fasting glucose levels controlling for comorbidities and sociodemographic factors. ResultsThe proportion of self-reported diabetes was 9.6%. The proportion of participants with ≥180mg/dl was 3.2% and that with ≥140mg/dl was 7.4%. Odds ratios indicated that self-reported diabetes was higher in older and obese groups and those who had hypertension and hypercholesterolemia and family history of diabetes, while elevated non-fasting glucose levels were higher among participants without health insurance and those who reported they had diabetes. ConclusionsVariability in risks between self-reported diabetes and measured glucose should be incorporated in diabetes self-care.