Family History of Diabetes is Associated with Increased Risk of Recurrent Diabetic Ketoacidosis in Pediatric Patients

Objective: To determine the relationship between family history of diabetes mellitus (DM) and diabetic ketoacidosis (DKA) recurrence in youth with established type 1 diabetes mellitus (T1DM).Methods: We performed a retrospective chart review of patients with DKA admitted to a pediatric hospital between January, 2009, and December, 2014. We compared patients with recurrent (≥2 admissions) and nonrecurrent DKA (1 admission) and investigated patient level factors, including family history, that may be associated with DKA recurrence in pediatric patients with established T1DM.Results: Of the 131 subjects in the study, 51 (39%) subjects were in the recurrence group. Age ≥15 years old, public health insurance, and family history of T1DM or type 2 diabetes mellitus were associated with recurrent DKA admissions in both univariable and multivariable analyses. Family history was associated with DKA recurrence, with an incidence rate ratio of 1.5 (95% confidence interval = 1.0 to 2.3; P = .03). The association was not explained by type of familial diabetes, first degree relative status, or whether the family member lived in the household.Conclusion: Recognition that a positive family history of DM may be associated with a higher risk for DKA recurrence in patients with established T1DM may allow for targeted education and focus on a previously unidentified population at increased risk for DKA. Understanding the mechanism underlying the effect of family history of diabetes on the rates of DKA in patients with established T1DM may allow for improved identification and education of patients who may be at risk for DKA recurrence.Abbreviations: CI = confidence interval; DKA = diabetic ketoacidosis; EHR = electronic health record; IBD = inflammatory bowel disease; IRR = incidence rate ratio; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus     

Potential Place of SGLT2 Inhibitors in Treatment Paradigms for type 2 Diabetes Mellitus

Objective: Following the first Food and Drug Administration (FDA) approval in 2013, sodium glucose cotransporter 2 (SGLT2) inhibitors have generated much interest among physicians treating patients with type 2 diabetes mellitus (T2DM). Here, the role in treatment with this drug class is considered in the context of T2DM treatment paradigms.Methods: The clinical trials for the SGLT2 inhibitors are examined with a focus on canagliflozin, dapagliflozin, and empagliflozin.Results: Evidence from clinical trials in patients with T2DM supports the use of SGLT2 inhibitors either as monotherapy or in addition to other glucose-lowering treatments as adjuncts to diet and exercise, and we have gained significant clinical experience in a relatively short time.Conclusion: The drugs appear to be useful in a variety of T2DM populations, contingent primarily on renal function. Most obviously, SGLT2 inhibitors appear to be well suited for patients with potential for hypoglycemia or weight gain. In clinical trials, patients treated with SGLT2 inhibitors have experienced moderate weight loss and a low risk of hypoglycemic events except when used in combination with an insulin secretagogue. In addition, SGLT2 inhibitors have been shown to reduce blood pressure, so they may be beneficial in patients with T2DM complicated by hypertension. SGLT2 inhibitors were incorporated into the 2015 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) position statement on the management of hyperglycemia and received an even more prominent position in the American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) comprehensive diabetes management guidelines and algorithm.Abbreviations: AE = adverse event A1C = glycated hemoglobin CI = confidence interval CKD = chronic kidney disease DKA = diabetic ketoacidosis DPP-4 = dipeptidyl peptidase 4 eGFR = estimated glomerular filtration rate FDA = Food and Drug Administration FPG = fasting plasma glucose GLP-1 = glucagon-like peptide 1 HDL-C = high-density lipoprotein cholesterol HR = hazard ratio LADA = late-onset autoimmune diabetes of adulthood LDL-C = low-density lipoprotein cholesterol MACE = major adverse cardiovascular events SGLT1 = sodium glucose cotransporter 1 SGLT2 = sodium glucose cotransporter 2 T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus UACR = urine albumin to creatinine ratio     

Risk Factors for Hypoglycemia in Inpatients with Total Parenteral Nutrition and Type 2 Diabetes: A Post HOC Analysis of the Insupar Study

Objective: Treatment of hyperglycemia with insulin is associated with increased risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients receiving total parenteral nutrition (TPN). The aim of this study was to determine the predictors of hypoglycemia in hospitalized T2DM patients receiving TPN.Methods: Post hoc analysis of the INSUPAR study, which is a prospective, open-label, multicenter clinical trial of adult inpatients with T2DM in a noncritical setting with indication for TPN.Results: The study included 161 patients; 31 patients (19.3%) had hypoglycemic events, but none of them was severe. In univariate analysis, hypoglycemia was significantly associated with the presence of diabetes with end-organ damage, duration of diabetes, use of insulin prior to admission, glycemic variability (GV), belonging to the glargine insulin group in the INSUPAR trial, mean daily grams of lipids in TPN, mean insulin per 10 grams of carbohydrates, duration of TPN, and increase in urea during TPN. Multiple logistic regression analysis showed that the presence of diabetes with end-organ damage, GV, use of glargine insulin, and TPN duration were risk factors for hypoglycemia.Conclusion: The presence of T2DM with end-organ damage complications, longer TPN duration, belonging to the glargine insulin group, and greater GV are factors associated with the risk of hypoglycemia in diabetic noncritically ill inpatients with parenteral nutrition.Abbreviations: ADA = American Diabetes Association; BMI = body mass index; CV% = coefficient of variation; DM = diabetes mellitus; GI = glargine insulin; GV = glycemic variability; ICU = intensive care unit; RI = regular insulin; T2DM = type 2 diabetes mellitus; TPN = total parenteral nutrition     

SARS-CoV-2 Seroprevalence in Individuals With Type 1 and Type 2 Diabetes Compared With Controls

ObjectiveData for the association between diabetes and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility are conflicting. We aimed to evaluate this association using an analytical cross-sectional study design.MethodsStudy participants were recruited from endocrine clinics of our hospital and belonged to 3 groups: group 1 (type 1 diabetes mellitus [T1DM]), group 2 (type 2 diabetes mellitus [T2DM]), and group 3 (controls). All participants submitted blood samples for SARS-CoV-2 S1/S2 immunoglobulin G antibody test (LIAISON; DiaSorin) and were interviewed for a history of documented infection.ResultsWe evaluated a total of 643 participants (T1DM, 149; T2DM, 160; control, 334; mean age, 37.9 ± 11.5 years). A total of 324 (50.4%) participants were seropositive for SARS-CoV-2. The seropositivity rate was significantly higher in the T1DM (55.7% vs 44.9%, P = .028) and T2DM (56.9% vs 44.9%, P = .013) groups than in the control group. The antibody levels in seropositive participants with T1DM and T2DM were not significantly different from those in seropositive controls. On multivariable analysis, low education status (odds ratio [OR], 1.41 [95% CI, 1.03-1.94]; P = .035), diabetes (OR, 1.68 [95% CI, 1.20-2.34]; P = .002), and overweight/obesity (OR, 1.52 [95% CI, 1.10-2.10]; P = .012) showed a significant association with SARS-CoV-2 seropositivity. The association between diabetes and SARS-CoV-2 seropositivity was found to further increase in participants with coexisting overweight/obesity (adjusted OR, 2.63 [95% CI, 1.54-4.47]; P < .001).ConclusionSARS-CoV-2 seropositivity, assessed before the onset of the national vaccination program, was significantly higher in participants with T1DM and T2DM than in controls. The antibody response did not differ between seropositive participants with and without diabetes. These findings point toward an increased SARS-CoV-2 susceptibility for patients with diabetes, in general, without any differential effect of the diabetes type.     

Efficacy of a simply resting box baited with crude fruit and leaf ethanol extracts of Phytolaccadodecandra (L’ Herit) in capturing and killing of indoor mosquitoes (Diptera: Culicidae) at Korando,Western Kenya

Effective capture and elimination of indoor resting mosquito population is important in the fight against mosquito borne diseases. This study aimed at evaluating the efficacy of a simply resting box baited with crude fruit and leaf ethanol extracts of Phytolacca dodecandra in attracting and killing indoor mosquitoes at Korando, Western Kenya. The study was conducted in three phases: pre-intervention, intervention and post intervention. Simple resting boxes made from galvanized wire frame measuring 30 cm × 30 cm × 30 cm, covered in blue and black tunic in and out and lined with carton boards were used. The boxes were baited with socks with strong human odour and 80 ml/100mls (e/w) solution of either crude ethanol fruit or leaf extracts of P. dodecandra, ethanol leaf extracts of Azadiracta indica or Deltamethrin. Deltamethrin and Azadiracta indica were used as positive and water as negative control. The treatments were applied at the intervention phase only. The boxes were left overnight in the houses and mosquitoes collected by 6.30 h. It was observed that more Culicines than Anopheline were captured irrespective of phase or treatment used. Mosquito densities reduced with phase of activity. P. dodecandra leaf extracts killed more mosquitoes than fruit or A. indica leaf extracts though the number were less than that of Deltamethrin or WHO threshold of >80% mortality. In conclusion, the simple resting boxes were effective in collecting and killing indoor mosquitoes though lethality did not matched the WHO threshold. With improved structural set up and use of pure extracts of P. dodecandra, the resting boxes can serve as effective tools for capture, elimination and management of mosquito borne diseases.     

Automated Insulin Delivery Systems as a Treatment for Type 2 Diabetes Mellitus: A Review

ObjectiveApproximately 6.3% of the worldwide population has type 2 diabetes mellitus (T2DM), and the number of people requiring insulin is increasing. Automated insulin delivery (AID) systems integrate continuous subcutaneous insulin infusion and continuous glucose monitoring with a predictive control algorithm to provide more physiologic glycemic control. Personalized glycemic targets are recommended in T2DM owing to the heterogeneity of the disease. Based on the success of hybrid closed-loop systems in improving glycemic control and safety in type 1 diabetes mellitus, there has been further interest in the use of these systems in people with T2DM.MethodsWe performed a review of AID systems with a focus on the T2DM population.ResultsIn 5 randomized controlled trials, AID systems improve time in range and reduce glycemic variability, without increasing insulin requirements or the risk of hypoglycemia.ConclusionAID systems in T2DM are safe and effective in hospitalized and closely monitored settings. Home studies of longer duration are required to assess for long-term benefit and identify target populations of benefit.     

Efficacy of a simply resting box baited with crude fruit and leaf ethanol extracts of Phytolaccadodecandra (L’ Herit) in capturing and killing of indoor mosquitoes (Diptera: Culicidae) at Korando,Western Kenya

Effective capture and elimination of indoor resting mosquito population is important in the fight against mosquito borne diseases. This study aimed at evaluating the efficacy of a simply resting box baited with crude fruit and leaf ethanol extracts of Phytolacca dodecandra in attracting and killing indoor mosquitoes at Korando, Western Kenya. The study was conducted in three phases: pre-intervention, intervention and post intervention. Simple resting boxes made from galvanized wire frame measuring 30 cm × 30 cm × 30 cm, covered in blue and black tunic in and out and lined with carton boards were used. The boxes were baited with socks with strong human odour and 80 ml/100mls (e/w) solution of either crude ethanol fruit or leaf extracts of P. dodecandra, ethanol leaf extracts of Azadiracta indica or Deltamethrin. Deltamethrin and Azadiracta indica were used as positive and water as negative control. The treatments were applied at the intervention phase only. The boxes were left overnight in the houses and mosquitoes collected by 6.30 h. It was observed that more Culicines than Anopheline were captured irrespective of phase or treatment used. Mosquito densities reduced with phase of activity. P. dodecandra leaf extracts killed more mosquitoes than fruit or A. indica leaf extracts though the number were less than that of Deltamethrin or WHO threshold of >80% mortality. In conclusion, the simple resting boxes were effective in collecting and killing indoor mosquitoes though lethality did not matched the WHO threshold. With improved structural set up and use of pure extracts of P. dodecandra, the resting boxes can serve as effective tools for capture, elimination and management of mosquito borne diseases.     

In vivo therapeutic exploring for Mori folium extract against type 2 diabetes mellitus in rats

Background: The study was aimed to investigate the potential therapeutic effect of Mori folium aqueous extracts (MFAE) on type 2 diabetes mellitus (T2DM) in vivo.Methods and results: A rat model of T2DM was established with the combination of high sugar and high-fat diet (HSFD) and streptozotocin (STZ). The T2DM rats were administrated with low (2 g.kg⁻¹) and high (5 g.kg⁻¹) doses of MFAE for 60 consecutive days. The biochemical indices of glucose metabolism disorders, insulin resistance and oxidative stress were observed. The results indicated that MFAE significantly promoted the synthesis of hepatic glycogen, reduced the levels of fasting blood glucose and fasting blood insulin, and improved the insulin sensitivity index (ISI). MFAE administration also remarkably increased the levels of superoxide dismutase (SOD) and reduced the levels of malondialdehyde (MDA).Conclusion: MFAE showed a therapeutic effect on T2DM with the bioative effect of improve glucose metabolism disorders, decrease insulin resistance, and ameliorate the antioxidative ability.     

Studies of naturally occurring friedelane triterpenoids as insulin sensitizers in the treatment type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a rapidly expanding public epidemic and frequently results in severe vascular complications. In an attempt to find anti-diabetic agents, we report herein on the isolation, structural elucidation and bioactivity of nine friedelane-type triterpenes (1–9) and twenty two known ones (10–31) from the root barks of Celastrus vulcanicola and Maytenus jelskii. Their structures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques. Two compounds from this series (1 and 3) exhibited increased insulin-mediated signalling, which suggests these friedelane triterpenes have potential therapeutic use in insulin resistant states.     

Metformin Use in Diabetes Prior to Hospitalization: Effects on Mortality in Covid-19

Objective: Although type 2 diabetes mellitus (T2DM) has been reported as a risk factor for coronavirus disease 2019 (COVID-19), the effect of pharmacologic agents used to treat T2DM, such as metformin, on COVID-19 outcomes remains unclear. Metformin increases the expression of angiotensin converting enzyme 2, a known receptor for severe acute respiratory syndrome coronavirus 2. Data from people with T2DM hospitalized for COVID-19 were used to test the hypothesis that metformin use is associated with improved survival in this population.Methods: Retrospective analyses were performed on de-identified clinical data from a major hospital in Wuhan, China, that included patients with T2DM hospitalized for COVID-19 during the recent epidemic. One hundred and thirty-one patients diagnosed with COVID-19 and T2DM were used in this study. The primary outcome was mortality. Demographic, clinical characteristics, laboratory data, diabetes medications, and respiratory therapy data were also included in the analysis.Results: Of these 131 patients, 37 used metformin with or without other antidiabetes medications. Among the 37 metformin-taking patients, 35 (94.6%) survived and 2 (5.4%) did not survive. The mortality rates in the metformin-taking group versus the non-metformin group were 5.4% (2/37) versus 22.3% (21/94). Using multivariate analysis, metformin was found to be an independent predictor of survival in this cohort (P = .02).Conclusion: This study reveals a significant association between metformin use and survival in people with T2DM diagnosed with COVID-19. These clinical data are consistent with potential benefits of the use of metformin for COVID-19 patients with T2DM.     

Cytochrome P450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes

Type 2 diabetes mellitus (T2DM) increases the risk of cognitive decline and dementia. Disruptions in the cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) pathway have been reported in T2DM, obesity and cognitive impairment. We examine linoleic acid (LA)-derived CYP450-sEH oxylipins and cognition in T2DM and explore potential differences between obese and nonobese individuals. The study included 51 obese and 57 nonobese participants (mean age 63.0 ± 9.9, 49% women) with T2DM. Executive function was assessed using the Stroop Color-Word Interference Test, FAS-Verbal Fluency Test, Digit Symbol Substitution Test, and Trails Making Test-Part B. Verbal memory was assessed using the California Verbal Learning Test, second Edition. Four LA-derived oxylipins were analyzed by ultra-high-pressure–LC/MS, and the 12,13-dihydroxyoctadecamonoenoic acid (12,13-DiHOME) considered the main species of interest. Models controlled for age, sex, BMI, glycosylated hemoglobin A1c, diabetes duration, depression, hypertension, and education. The sEH-derived 12,13-DiHOME was associated with poorer executive function scores (F_1,98 = 7.513, P = 0.007). The CYP450-derived 12(13)-epoxyoctadecamonoenoic acid (12(13)-EpOME) was associated with poorer executive function and verbal memory scores (F_1,98 = 7.222, P = 0.008 and F_1,98 = 4.621, P = 0.034, respectively). There were interactions between obesity and the 12,13-DiHOME/12(13)-EpOME ratio (F_1,97 = 5.498, P = 0.021) and between obesity and 9(10)-epoxyoctadecamonoenoic acid (9(10)-EpOME) concentrations (F_1,97 = 4.126, P = 0.045), predicting executive function such that relationships were stronger in obese individuals. These findings suggest that the CYP450-sEH pathway as a potential therapeutic target for cognitive decline in T2DM. For some markers, relationships may be obesity dependent.     

Preclinical Characterization of Recombinant Human Tissue Kallikrein-1 as a Novel Treatment for Type 2 Diabetes Mellitus

Modulation of the kallikrein-kinin system (KKS) has been shown to have beneficial effects on glucose homeostasis and several other physiological responses relevant to the progression of type 2 diabetes mellitus (T2D). The importance of bradykinin and its receptors in mediating these responses is well documented, but the role of tissue kallikrein-1, the protease that generates bradykinin in situ, is much less understood. We developed and tested DM199, recombinant human tissue kallikrein-1 protein (rhKLK-1), as a potential novel therapeutic for T2D. Hyperinsulinemic-euglycemic clamp studies suggest that DM199 increases whole body glucose disposal in non-diabetic rats. Single-dose administration of DM199 in obese db/db mice and ZDF rats, showed an acute, dose-dependent improvement in whole-body glucose utilization. Sub-acute dosing for a week in ZDF rats improved glucose utilization, with a concomitant rise in fasting insulin levels and HOMA1-%B scores. After cessation of sub-acute dosing, fasting blood glucose levels were significantly lower in ZDF rats during a drug wash-out period. Our studies show for the first time that DM199 administration results in acute anti-hyperglycemic effects in several preclinical models, and demonstrate the potential for further development of DM199 as a novel therapeutic for T2D.     

1,5-Anhydroglucitol and Neonatal Complications in Pregnancy Complicated by Diabetes

Objective: To determine the association of 1,5-anhydroglucitol (1,5-AG) with neonatal birth weight (NBW) and neonatal hypoglycemia (+NH) in pregnancies complicated by diabetes.Methods: We assessed a retrospective cohort of 102 females, 17 with gestational diabetes (GDM), 48 with type 1 diabetes mellitus (T1DM), and 37 with type 2 diabetes mellitus (T2DM). 1,5-AG and glycated hemoglobin A1C (A1C) values throughout pregnancy were extracted. Linear regression was used to assess their association with NBWs z-scores adjusting for maternal age, ethnicity and body mass index (BMI). +NH was defined by a note in the infant record, glucose <1.7 mmol/L in the first 24 h, or <2.5 mmol/L in the first 48 h after birth. A t test or Welch's approximate t test was used to compare the mean 1,5-AG and A1C of mothers with +NH versus those without (-NH), adjusted for gestational age and analyzed by diabetes type and across trimesters.Results: Mean 1,5-AG significantly differed across groups: T1DM 3.77 ± 2.82 μg/mL, T2DM 5.73 ± 4.38 μg/mL, GDM 8.89 ± 4.39 μg/mL (P<.0001), suggesting less glucose exposure in GDM relative to T1DM or T2DM. A negative linear association was found between mean 1,5-AG and z-scores (R= -0.28, P = .005. In contrast, the association between mean A1C and z-scores was weaker (R = 0.15, P = .14). The mean 1,5-AG tended to be lower in the +NH cohort versus -NH (P = .08), and this was statistically significant (P = .01) among subjects with GDM.Conclusion: The association of 1,5-AG with complications related to glycemic exposure supports the notion of its utility as an adjunct glycemic biomarker in pregnancies complicated by diabetes and across trimesters.Abbreviations: 1,5-AG = 1,5-anhydroglucitol A1C = glycated hemoglobin A1C BMI = body mass index CGM = continuous glucose monitoring GDM = gestational diabetes mellitus LGA = large for gestational age MICC = maternal and infant care unit NBW = neonatal birth weight NH = neonatal hypoglycemia PPH = postprandial hyperglycemia SMBG = self-monitoring of blood glucose T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus     

Inhibition of Renal Glucose Reabsorption: A Novel Strategy for Achieving Glucose Control in Type 2 Diabetes Mellitus

ObjectiveTo review the renal handling of glucose and the role of inhibition of a sodium-glucose transporter (SGLT2) in the treatment of type 2 diabetes mellitus (T2DM).MethodsWe review the published data about (1) the filtration and reabsorption of glucose by the kidneys in normal subjects and patients with diabetes; (2) the deleterious effects of long-term elevation of plasma glucose levels on muscle and hepatic insulin sensitivity and beta cell function (that is, glucotoxicity); (3) the effect of inhibiting the SGLT2 transporter on the induction of glycosuria, glycemic control, insulin resistance, and beta cell dysfunction in animals and humans with diabetes; and (4) the safety of SGLT2 inhibition as a therapeutic modality to treat human T2DM.ResultsStudies in animal models of diabetes document the efficacy of the SGLT2 inhibitors in inducing glycosuria, decreasing both fasting and postprandial glucose levels, augmenting beta cell function, and enhancing hepatic and muscle insulin sensitivity. In human T2DM, short-term studies with dapagliflozin (12 weeks) and sergliflozin (2 weeks) have confirmed the efficacy of these agents in improving glycemic control. Excessive urinary electrolyte or water loss, plasma electrolyte disturbances, and hypoglycemia were not observed.ConclusionSGLT2 inhibitors represent a promising approach to the treatment of T2DM. They have the potential to be used as monotherapy, as well as in combination with all approved antidiabetic agents. Because their mechanism of action is independent of the severity of beta cell dysfunction or insulin resistance, efficacy should not decline with progressive beta cell failure or in the presence of severe insulin resistance. (Endocr Pract. 2008;14:782-790)     

Diversified Microbiota of Meconium Is Affected by Maternal Diabetes Status

Objectives

This study was aimed to assess the diversity of the meconium microbiome and determine if the bacterial community is affected by maternal diabetes status.

Methods

The first intestinal discharge (meconium) was collected from 23 newborns stratified by maternal diabetes status: 4 mothers had pre-gestational type 2 diabetes mellitus (DM) including one mother with dizygotic twins, 5 developed gestational diabetes mellitus (GDM) and 13 had no diabetes. The meconium microbiome was profiled using multi-barcode 16S rRNA sequencing followed by taxonomic assignment and diversity analysis.

Results

All meconium samples were not sterile and contained diversified microbiota. Compared with adult feces, the meconium showed a lower species diversity, higher sample-to-sample variation, and enrichment of Proteobacteria and reduction of Bacteroidetes. Among the meconium samples, the taxonomy analyses suggested that the overall bacterial content significantly differed by maternal diabetes status, with the microbiome of the DM group showing higher alpha-diversity than that of no-diabetes or GDM groups. No global difference was found between babies delivered vaginally versus via Cesarean-section. Regression analysis showed that the most robust predictor for the meconium microbiota composition was the maternal diabetes status that preceded pregnancy. Specifically, Bacteroidetes (phyla) and Parabacteriodes (genus) were enriched in the meconium in the DM group compared to the no-diabetes group.

Conclusions

Our study provides evidence that meconium contains diversified microbiota and is not affected by the mode of delivery. It also suggests that the meconium microbiome of infants born to mothers with DM is enriched for the same bacterial taxa as those reported in the fecal microbiome of adult DM patients.     

Dexamethasone Stress Test: A Pilot Clinical Study for Identification of Individuals Highly Prone to Develop Type 2 Diabetes

Objective: We examined whether the “Dexamethasone Stress Test” exhibits the requisite high predictive ability to identify individuals highly prone to develop type 2 diabetes mellitus (T2DM).Methods: Seven years ago, we administered an oral glucose tolerance test (OGTT) to 33 individuals without T2DM and repeated the OGTT 24 hours after a single oral dose of 8 mg dexamethasone (Dex); all participants had a first-degree relative with T2DM, and close to half had prediabetes. We calculated receiver operating characteristic (ROC) curves for all parameters derived from the OGTT before and after Dex in individuals who subsequently developed diabetes compared to individuals who did not.Results: At 7 years of follow-up, 9 individuals had developed T2DM, while 24 remained without diabetes. None of the OGTT-derived parameters before administration of Dex had an area under the ROC curve of >0.8. However, 24 hours after Dex, three parameters, including fasting plasma insulin, homeostatic model assessment–insulin resistance, and 2-hour plasma glucose level, exhibited areas under the ROC curves of 0.84, 0.86, and 0.92, respectively.Conclusion: The Dexamethasone Stress Test appears to be a good to excellent test in identifying individuals highly prone to develop T2DM.Abbreviations: AUC = area under the curve; Dex = dexamethasone; HOMA-IR = homeostatic model assessment–insulin resistance; NGT = normal glucose tolerance; OGTT = oral glucose tolerance test; PreDiab = prediabetes; ROC = receiver operating characteristic; T2DM = type 2 diabetes mellitus     

膀胱尿路上皮肿瘤合并2型糖尿病患者临床和病理特点的比较性研究

目的:对比分析膀胱尿路上皮肿瘤合并2型糖尿病患者的临床和病理特点,为临床诊疗工作提供一定的参考。方法:回顾性分析2015年1月至2019年2月于我院泌尿外科手术治疗且经病理确诊为原发性膀胱尿路上皮肿瘤的患者资料,合并2型糖尿病的膀胱肿瘤患者59例设为糖尿病组(T2DM组),根据性别和年龄按照1:2的比例匹配同时期未合并2型糖尿病的膀胱肿瘤118例患者为非糖尿病组(NT2DM组),比较两组患者的临床特征和病理特点。结果:T2DM组的高血压患者比例和血肌酐值高于NT2DM组(P<0.05),而在教育程度、吸烟、饮酒、BMI、前列腺增生、泌尿系感染、血常规、肝功、尿常规、肿瘤大小、数量方面无明显统计学差异(P>0.05)。T2DM组和NT2DM组在膀胱尿路上皮肿瘤良恶性分类、肿瘤数量、肿瘤大小的构成比上无明显统计学差异(P>0.05);然而,对膀胱恶性肿瘤患者进行亚组分析显示,T2DM亚组中肌层浸润性癌的比例和高级别癌的比例明显高于NT2DM亚组,差异有统计学意义(P<0.05)。结论:2型糖尿病可能使膀胱癌的病理分级和分期更高,导致患者预后更差,临床上应更加关注膀胱恶性肿瘤合并2型糖尿病患者的诊治。     

Glycemic Control and Diabetic Dyslipidemia in Adolescents with Type 2 Diabetes

ObjectiveThe incidence of type 2 diabetes mellitus (T2DM) is increasing at an alarming rate, especially in ethnic minorities, and T2DM is associated with significant comorbidities. The primary objective of this study was to assess glycemic control and cardiovascular risk outcomes in children with T2DM at 1 year after diagnosis. We also assessed whether insulin treatment at onset of diabetes is beneficial for overall outcome in those with elevated glycated hemoglobin (HbA1C).MethodsA retrospective electronic chart review of non-Hispanic white (NHW) and African American (AA) children with T2DM.ResultsA total of 86 patients (66.3% females, 79.1% AA, mean age, 13.8 ± 2.4 years) with T2DM were included. Analyses of therapeutic outcome measures at the 1-year follow-up showed HbA1C <8% in 27.7% of patients, low-density-lipoprotein cholesterol (LDL-C) >130 mg/dL in 12.5%, non-high-density-lipoprotein cholesterol (non-HDL-C) >160 mg/dL in 15.6%, HDL-C <35 mg/dL in 25%, systolic hypertension (HTN) in 35.6%, and diastolic HTN in 6.8% of subjects. Among those started on insulin at initial diagnosis, there was significant improvement in glycemic outcomes (P<.0001 on insulin vs. P = .02 not on insulin) and dyslipidemia (total cholesterol [TC] [P = .001], LDL-C [P = .02], HDL-C [P = .01], non-HDL-C [P = .0002], and TC/HDL-C [P = .005]) compared with no significant change among those who did not receive insulin at diagnosis.ConclusionSubstantial numbers of children with T2DM do not achieve glycemic and cardiovascular therapeutic goals 1 year after diagnosis. Insulin therapy at diagnosis has significant beneficial effects on diabetic dyslipidemia in those with higher HbA1C. (Endocr Pract. 2013; 19:972-979)     

Clinical Efficacy of Stem Cell Therapy for Diabetes Mellitus: A Meta-Analysis

BackgroundStem cell therapy is a promising therapeutic modality for advanced diabetes mellitus (DM). This study presents a meta-analysis of relevant clinical trials to determine the efficacy of stem cell therapy in DM. We aim to critically evaluate and synthesize clinical evidence on the safety and efficiency of different types of stem cell therapy for both T1DM and T2DM.ConclusionsStem cell transplantation can represent a safe and effective treatment for selected patients with DM. In this cohort of trials, the best therapeutic outcome was achieved with CD34⁺ HSC therapy for T1DM, while the poorest outcome was observed with HUCB for T1DM. Diabetic ketoacidosis impedes therapeutic efficacy.     

Cell Treatment for Stroke in Type Two Diabetic Rats Improves Vascular Permeability Measured by MRI

Treatment of stroke with bone marrow stromal cells (BMSC) significantly enhances brain remodeling and improves neurological function in non-diabetic stroke rats. Diabetes is a major risk factor for stroke and induces neurovascular changes which may impact stroke therapy. Thus, it is necessary to test our hypothesis that the treatment of stroke with BMSC has therapeutic efficacy in the most common form of diabetes, type 2 diabetes mellitus (T2DM). T2DM was induced in adult male Wistar rats by administration of a high fat diet in combination with a single intraperitoneal injection (35mg/kg) of streptozotocin. These rats were then subjected to 2h of middle cerebral artery occlusion (MCAo). T2DM rats received BMSC (5x10⁶, n = 8) or an equal volume of phosphate-buffered saline (PBS) (n = 8) via tail-vein injection at 3 days after MCAo. MRI was performed one day and then weekly for 5 weeks post MCAo for all rats. Compared with vehicle treated control T2DM rats, BMSC treatment of stroke in T2DM rats significantly (p<0.05) decreased blood-brain barrier disruption starting at 1 week post stroke measured using contrast enhanced T₁-weighted imaging with gadopentetate, and reduced cerebral hemorrhagic spots starting at 3 weeks post stroke measured using susceptibility weighted imaging, although BMSC treatment did not reduce the ischemic lesion volumes as demarcated by T₂ maps. These MRI measurements were consistent with histological data. Thus, BMSC treatment of stroke in T2DM rats initiated at 3 days after stroke significantly reduced ischemic vascular damage, although BMSC treatment did not change infarction volume in T2DM rats, measured by MRI.