History Of T2DM Research Articles

Management Dilemma: A Case of Acute Epiglottitis Secondary to Group A Streptococcus (GAS)

SESSION TITLE: Shock SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: In adults, epiglottitis has a male preponderance with the potential for rapid airway obstruction. Risk factors include hypertension, diabetes mellitus (T2DM), substance abuse and immune deficiency. CASE PRESENTATION: A 52-year-old male with history of T2DM, obesity and alcohol abuse presented with shortness of breath and choking sensation. Intubation was attempted in the ER for respiratory distress using a size 6 endotracheal tube. Chest X-ray revealed poor tube position despite multiple attempts to advance it. Epinephrine and pulse steroids were administered. Emergent bronchoscopy showed swelling of the supraglottis and an emergent tracheostomy was performed. Labs revealed leukocytosis with bandemia. Neck CT scan confirmed acute epiglottitis with critical airway stenosis. Bronchoalveolar lavage and blood cultures grew GAS. Bacteremia cleared two days after admission with Ceftriaxone and Vancomycin. Patient had spiking fevers and was noted to be extremely agitated. He received steroids for five days after a second CT neck revealed no interval change in edema.(Image 2) Two weeks after persistent fevers and hemodynamic instability requiring pressors, antibiotics were switched to Penicillin (PCN) G and Clindamycin without resuming steroids. After 24 hours, patient had significant clinical improvement and was subsequently weaned off the ventilator. He was seen in the clinic after discharge with complete resolution of symptoms. DISCUSSION: Multiple retrospective studies have noted that epiglottitis in adults can be managed conservatively with airway support required in only 6.6 - 16% of patients. We encountered a severe case of acute epiglottitis in an adult male who failed to respond clinically after two weeks of appropriate antibiotic coverage and a trial of steroids but responded to the addition of Clindamycin. The loss of penicillin binding proteins in ‘stationary growth phase’ bacteria occurs in more invasive streptococcal infections rendering PCNs less effective. Clindamycin suppresses bacterial toxin production, enhances opsonization, decreases cytokine activation and has a post-antibiotic effect.1 A recent in-vivo and in-vitro study endorsed the addition of Clindamycin to PCN in severe streptococcal infections.2 CONCLUSIONS: GAS epiglottitis can present in adults with risk factors: male sex, diabetics and substance abuse. With poor clinical response, complications such as toxic shock syndrome should be considered. The addition of Clindamycin to PCN in severe streptococcal infections may be beneficial with its action on slow growing bacteria and ability to inhibit bacterial toxin production. Reference #1: 1.Russell NE, Pachorek RE. Clindamycin in the treatment of streptococcal and staphylococcal toxic shock syndromes. Ann Pharmacother. 2000;34(7-8):936-939. Reference #2: 2.Andreoni F, Zürcher C, Tarnutzer A, et al. Clindamycin Affects Group A Streptococcus Virulence Factors and Improves Clinical Outcome. J Infect Dis. 2016;1:jiw229. DISCLOSURE: The following authors have nothing to disclose: Hisham Hakeem, Marnie Aguasvivas, Lokesh Dayal, Killol Patel No Product/Research Disclosure Information

Inflammatory and oxidative stress‑associated factors in chronic intermittent hypoxia in Chinese patients, rats, lymphocytes and endotheliocytes.

In order to investigate the association between inflammatory and oxidative stress (OS)-associated factors in chronic intermittent hypoxia (CIH), 238 CIH patients and 156 healthy volunteers were included. CIH rat and lymphocytes were used as experimental models. Interleukin (IL)-6, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), nitric oxide (NO) and nitric oxide synthase (NOS) were analyzed. Patients with CIH were older, with hypertension, increased heart rate (HR) and body mass index (BMI), and there were more males than females. Those with a history of smoking or type 2 diabetes (T2DM) history exhibited an increased risk of CIH. Serum IL-6, TNF-α and CRP in patients with CIH were increased, while NO and NOS were decreased. Hakka patients exhibited increased BMI measurements and NO expression, and decreased systolic arterial pressure, IL-6 and TNF-α compared with non-Hakka patients. Rats with CIH exhibited hypertension and stable weight, less activity and decreased appetite, increased HR and serum IL-6, TNF-α and CRP, and decreased NO and NOS. IL-6, TNF-α, CRP, NO and induced-NOS (iNOS) were increased in the lymphocytes of CIH rats compared with healthy ones. In rat endotheliocytes induced by CIH, IL-6, TNF-α, CRP and iNOS increased, while NO and endothelial-NOS (eNOS) decreased. In the supernatant of co-cultured lymphocytes and endotheliocytes, IL-6, TNF-α and CRP increased, although NO and NOS decreased. In conclusion, age, male gender, BMI, smoking and T2DM history, serum IL-6, TNF-α and CRP were positively correlated with CIH combined with hypertension, while NO and NOS were negatively correlated with CIH. Serum NO was predominantly synthesized and released by eNOS. Hakka patients exhibited decreased inflammation and OS with CIH. Increasing IL-6, TNF-α and CRP, and decreasing NO and NOS are biomarkers of CIH, which could be targets in diagnosis, treatment and prevention of CIH.

Polymorphism in ERCC1 confers susceptibility of coronary artery disease and severity of coronary artery atherosclerosis in a Chinese Han population

Excision repair cross-complementing 1 (ERCC1) gene encodes ERCC1 protein, which is mainly responsible for the repair of DNA damage in different diseases including coronary artery atherosclerosis by acting as a rate-limiting element in nucleotide excision repair (NER). Using a three-stage case-control study with 3037 coronary artery disease (CAD) patients and 3002 controls, we investigated associations of three single nucleotide polymorphisms (SNPs) with CAD risk and severity of coronary artery atherosclerosis in Chinese Han population. In the discovery set, the variant allele T of rs11615 was significantly associated with higher CAD risk (adjusted OR = 1.27, P = 0.006) and severity of coronary artery atherosclerosis (adjusted OR = 1.54, P = 0.003). These associations were more remarkable in the merged set (adjusted OR = 1.23, P = 8 × 10−6 for CAD risk; adjusted OR = 1.36, P = 4.3 × 10−5 for severity of coronary artery atherosclerosis). And the expression level of ERCC1 was significantly higher in CAD cases than controls. Multiplicative interactions among SNP rs11615, alcohol drinking, history of T2DM, and history of hyperlipidemia could increase 5.06-fold risk of CAD (P = 1.59 × 10−9). No significant association of rs2298881 and rs3212986 with CAD risk was identified. Taken together, SNP rs11615 in ERCC1 gene might confer susceptibility to CAD and severity of coronary atherosclerosis in a Chinese Han population.

Risk score model of type 2 diabetes prediction for rural Chinese adults: the Rural Deqing Cohort Study.

Risk score (RS) model is a cost-effective tool to identify adults who are at high risk for diabetes. This study was to develop an RS model of type 2 diabetes (T2DM) prediction specifically for rural Chinese adults. A prospective whole cohort study (n=28,251) and a sub-cohort study (n=3043) were conducted from 2006-2014 and 2006-2008 to 2015 in rural Deqing, China. All participants were free of T2DM at baseline. Incident T2DM cases were identified through electronic health records, self-reported and fasting plasma glucose testing for the sub-cohort, respectively. RS models were constructed with coefficients (β) of Cox regression. Receiver-operating characteristic curves were plotted and the area under the curve (AUC) reflected the discriminating accuracy of an RS model. By 2015, the incidence of T2DM was 3.3 and 7.7 per 1000 person-years in the whole cohort and the sub-cohort, respectively. Based on data from the whole cohort, the non-invasive RS model included age (4 points), overweight (2 points), obesity (4 points), family history of T2DM (3 points), meat diet (3 points), and hypertension (2 points). The plus-fasting plasma glucose (FPG) model added impaired fasting glucose (4 points). The AUC was 0.705 with a positive predictive value of 2.5% for the non-invasive model, and for the plus-FPG model the AUC was 0.754 with a positive predictive value of 2.5%. These models performed better as compared with 12 existing RS models for the study population. Our non-invasive RS model can be used to identify individuals who are at high risk of T2DM as a simple, fast, and cost-effective tool for rural Chinese adults.

Diabetes mellitus: an important risk factor for reactivation of tuberculosis.

SummaryDiabetes mellitus was identified as a risk factor for developing tuberculosis (TB) infection, and relapse after therapy. The risk of acquiring TB is described as comparable to that of HIV population. The fact that diabetics are 3× times more prone to develop pulmonary TB than nondiabetics cannot be overlooked. With DM recognized as global epidemic, and TB affecting one-third of the world population, physicians must remain vigilant. We present a 45-year-old woman born in Dominican Republic (DR), with 10-year history of T2DM treated with metformin, arrived to our Urgency Room complaining of dry cough for the past 3months. Interview unveiled unintentional 15lbs weight loss, night sweats, occasional unquantified fever, and general malaise but denied bloody sputum. She traveled to DR 2years before, with no known ill exposure. Physical examination showed a thin body habitus, otherwise well appearing woman with stable vital signs, presenting solely right middle lung field ronchi. LDH, ESR, hsCRP and Hg A1C were elevated. Imaging revealed a right middle lobe cavitation. Sputum for AFB disclosed active pulmonary TB. Our case portrays that the consideration of TB as differential diagnosis in diabetics should be exercised with the same strength, as it is undertaken during the evaluation of HIV patients with lung cavitation. Inability to recognize TB will endanger the patient, hospital dwellers and staff, and perpetuate this global public health menace.Learning pointsDiabetes mellitus should be considered an important risk factor for the reactivation of pulmonary tuberculosis.High clinical suspicious should be taken into consideration as radiological findings for pulmonary tuberculosis in patients with diabetes mellitus may be atypical, involving middle and lower lobes.Inability to recognize pulmonary tuberculosis will endanger the patient, hospital dwellers and staff, and perpetuate this global public health menace.

Combination Tratment of Oral Agents and Insulin in Type 2 Diabetes: A Narrative Review

Type 2 diabetes (T2DM) necessitates early and effective treatment to delay or prevent micro- and macrovascular complications associated with diabetes. Monotherapy often fails after a period of treatment, so that multiple drugs are needed to achieve effective glycemic control. It is known that insulin is very effective in reducing hyperglycemia and may improve β-cell function in patients with T2DM. Based on the improved understanding of the pathophysiology and natural history of T2DM, insulin therapy should be introduced sooner rather than later to sustain glycemic targets. Adding oral antidiabetic drugs (OAD) to insulin can improve glycemic control and potentially lower the required insulin dose, resulting in less weight gain and lower risk for hypoglycemia. The treatto-target algorithms of the recent studies combining OADs plus insulin have demonstrated that patients can reach glycemic treatment targets with low risk of hypoglycemia, greater convenience and with limited weight gain. This article presents the pharmacologic and physiologic aspects of combination treatment of oral agents with insulin in T2DM and elaborates current options available for this combination therapy. The evidence along with potential advantages and drawbacks of such regimens are discussed.

The role of vitamin D, obesity and physical exercise in regulation of glycemia in Type 2 Diabetes Mellitus patients

AimThe aims of this study were to determine the role of vitamin D, obesity and physical exercise in the regulation of glycemia in Type 2 Diabetes Mellitus patients in a highly consanguineous population. DesignCase and control study. SettingThe survey was carried out at the Hamad General Hospital and Primary Health Care (PHC) centers in the State of Qatar. SubjectsThe study was conducted from November 2012 to June 2014 among subjects above 30 years of age. Of the 2224 registered with diagnosed diabetes and free diseases attending Hamad General Hospital and PHC centers agreed and gave their consent to study. MethodsQuestionnaire included socio-demographic variables, body mass index (BMI), consanguinity, lifestyle habits, family history of diabetes, blood pressure and development of diabetes complications such as retinopathy, nephropathy, and neuropathy were collected at regular intervals throughout the follow-up. Univariate and multivariate statistical analysis were performed. ResultsThere were statistically significant difference between patients with diabetic and control in terms of ethnicity (p=0.012), level of education (p=0.002), occupation (p<0.001), monthly income (p<0.001), BMI(p=0.024), sport activity (p=0.018), cigarette smoking (p<0.001), consanguinity (p=0.029) and family history of Diabetes Mellitus (p<0.001) and co-morbidity hypertension (p=0.041). Further, the biochemistry values in the studied subjects with T2DM compared to healthy controls and the study revealed that serum Vitamin D, BMI, fasting glucose level, calcium, HbA1c, total cholesterol HDL, LDL, bilirubin, triglycerides, uric acid and blood pressure systolic and diastolic were higher in T2DM compared to their counterparts. Multivariate logistic regression showed that vitamin D deficiency ng/mL, Family History of T2DM, BMI (kg/m2) hypertension, consanguinity, income, mother occupation, ethnicity, educational level and Lack of physical exercise variables were significant predictors of diabetes. In the group of Diabetes Mellitus Type 2 patients, 39.3% as opposed to 51.2% in the control group had vitamin D deficiency, 25(OH) D3 levels≤10ng/ml (p<0.001). In the group of Diabetes Mellitus Type 2 patients, 34.6% as opposed to 37.9% in the control group had vitamin D insufficiency, 25(OH)D3 levels <20ng/ml (p < 0.001). In the group of Diabetes Mellitus Type 2 patients, 22.8% as opposed to 14.2% in the control group had vitamin D sufficiency, 25(OH)D3 levels >30 10ng/ml (p < 0.001). ConclusionVitamin D, family history of diabetes, consanguinity marriages’ and hereditary gene-environment interactions and physical exercise may also contribute to the current diabetes epidemic in Qatari’s Arab populations.

Impact of a health educational guidelines on the knowledge, self-management practice and self-efficacy of patients with type-2 diabetes

Background: Diabetes is a common costly condition associated with significant morbidity and mortality. The process of teaching individuals to manage their diabetes had been considered an important part of the clinical management. The goals of self-management education are to optimize metabolic control, prevent acute and chronic complications, and optimize quality of life; Aim: To evaluate the impact of a health education intervention guidelines for T2DM on Patients’ knowledge, self-efficacy, and self-management practices. Methods: Design: quasi-experimental uncontrolled design on 50 patients evaluated at pre-intervention, post-intervention, and 6-month follow-up. Setting: The study was carried out in the outpatient clinics of Endocrinology and Metabolism at Zagazig University Hospital. Tools: three tools were used, 1st tool was an interview questionnaire to assess socio-demographic data and patients’ knowledge, self-efficacy scale and patients’ self-reported self-management behaviors concerning self-care practices. Results: There were statistically significant improvements in patients’ knowledge ( p < .001), self-efficacy ( p < .001), and selfmanagement ( p < .001), which continued through follow-up. Multivariate analysis showed that the knowledge and self-efficacyscores positively predicted the scores of self-management. Conclusions: The study demonstrates the effectiveness of health educational intervention guidelines in improving T2DM patients’self-management behaviors and self-care practices through provision of sound information and fostering their self-efficacy. The slight decline at the follow-up phase indicates the need for periodic booster doses of the intervention. Therefore, the study recommends generalization of such educational guidelines in all health care settings providing services to T2DM patients. Such guidelines should particularly address the patients with low educational attainments, long history of T2DM, and those residing in rural areas. More research is needed to investigate the long-term effect of such educational interventions.

Adiponectin levels predict prediabetes risk: the Pathobiology of Prediabetes in A Biracial Cohort (POP-ABC) study

BackgroundAdiponectin levels display ethnic disparities, and are inversely associated with the risk of type 2 diabetes (T2DM). However, the association of adiponectin with prediabetes risk in diverse populations has not...

Low Cardiorespiratory Fitness Is Associated with Markers of Insulin Resistance in Young, Normal Weight, Hispanic Women.

Low cardiorespiratory fitness (CRF) and its decline over time are predictors of the development of diabetes in black and Caucasian women, independent of obesity. It is unclear, however, if the adverse effect of low CRF on the risk of diabetes in Hispanic women is mediated by obesity. Our purpose was to determine the associations of CRF with markers of insulin resistance in 68 normal weight Hispanic women. Obesity indicators included body mass index (BMI), body composition by DXA, and waist circumference. CRF was measured by indirect calorimetry. A glucose tolerance test was used to measure markers of insulin resistance: homeostasis model assessment, fasting insulin, 2-hr insulin, area under the curve insulin, qualitative insulin sensitivity check, and insulin sensitivity index. Pearson correlation and multiple regression analyses were used to identify associations between CRF and markers of insulin resistance. Multivariate ANOVA was used to compare markers of insulin resistance over quartiles of CRF. Low CRF was significantly associated with all markers of insulin resistance (P < 0.01). These associations were independent of age, BMI, waist circumference, family history of T2DM, and triglycerides (CRF standardized beta range: -0.27 to -0.46, P < 0.05). However, these associations were attenuated when body composition, specifically fat-free mass, was entered into the model (CRF standardized beta range: -0.03 to 0.21, P > 0.05). All markers of insulin resistance improved linearly across CRF quartiles (P < 0.05). Our findings suggest that low CRF may be an important predictor of diabetes risk in Hispanic women and that fat-free mass rather than overall body adiposity mediates these relationships.

Maternal and Paternal Transmission of Diabetes: Influence of Nutritional Factors

Background: Pakistan is ranked at 6th place amongst the top 10 countries of the world. The number of estimated cases with diabetes in our country are 5.2 million in 2000 and projected to be 13.9 million in 2003. The objective of this research to examined risk for 2 diabetes and conditioned on directly ascertained parental diabetes status among population of Karachi, Pakistan. Methodology: This was a cross-sectional study. Young healthy subjects between 18- 24 years were inducted. They were classified according to familial history of T2DM as Single Diabetic Parent (SDP), with Both Diabetic Parents (BDP) and with No Diabetic Parents (NDP). Anthropometric measurements where BMI (Body Mass Index) and WHR (Waist Hip Ratio) was assesed and Fasting plasma glucose was analyzed by photometric technique. Results: Paternal transmission of diabetes is 73.2% and Maternal was 26.8% in our population. Significantly higher statistical values were observed in the body weight of offspring of both diabetics as compared to NDP and SDP. Mean values for BMI among BDP were 25.58 ± 5.15, 22.26 ± 6.80 in SDP and NDP it was 21.02 ± 6.19 and 4.91 ± 6.78. BDP offspring showed high risk of WHR for males i.e 14.3% and for females it was 37.5%, and SDP offsprings had 23.1% in males and 30.4% in females, whereas offsprings of NDP had a normal WHR. Conclusion: Family history of diabetes in offsprings is an insight of developing diabetes in future offspring. We determined the parental transmission of diabetes mellitus in our population and evaluated its influence on BMI, WHR and Fasting plasma glucose. There was a raised frequency of paternal history of diabetes as compared to maternal history. Anthropometric measurements and Fasting Plasma glucose are the predicting factors contributing to T2DM in subjects who have diabetic parents, either single or both diabetic.

American Association Of Clinical Endocrinologists, American College Of Endocrinology, And Androgen Excess And Pcos Society Disease State Clinical Review: Guide To The Best Practices In The Evaluation And Treatment Of Polycystic Ovary Syndrome - Part 2

Polycystic ovary syndrome (PCOS) is recognized as the most common endocrine disorder of reproductive-aged women around the world. This document, produced by the collaboration of the American Association of Clinical Endocrinologists and the Androgen Excess Society aims to highlight the most important clinical issues confronting physicians and their patients with PCOS. It is a summary of current best practices in 2014. Insulin resistance is believed to play an intrinsic role in the pathogenesis of PCOS. The mechanism by which insulin resistance or insulin give rise to oligomenorrhea and hyperandrogenemia, however, is unclear. Hyperinsulinemic-euglycemic clamp studies have shown that both obese and lean women with PCOS have some degree of insulin resistance. Insulin resistance is implicated in the ovulatory dysfunction of PCOS by disrupting the hypothalamic-pituitary-ovarian axis. Given the association with insulin resistance, all women with PCOS require evaluation for the risk of metabolic syndrome (MetS) and its components, including type 2 diabetes, hypertension, hyperlipidemia, and the possible risk of clinical events, including acute myocardial infarction and stroke. Obese women with PCOS are at increased risk for MetS with impaired glucose tolerance (IGT; 31 to 35%) and type 2 diabetes mellitus (T2DM; 7.5 to 10%). Rates of progression from normal glucose tolerance to IGT, and in turn to T2DM, may be as high as 5 to 15% within 3 years. Data suggest the need for baseline oral glucose tolerance test every 1 to 2 years based on family history of T2DM as well as body mass index (BMI) and yearly in women with IGT. Compared with BMI- and age-matched controls, young, lean PCOS women have lower high-density lipoprotein (HDL) size, higher very-low-density lipoprotein particle number, higher low-density lipoprotein (LDL) particle number, and borderline lower LDL size. Statins have been shown to lower testosterone levels either alone or in combination with oral contraceptives (OCPs) but have not shown improvement in menses, spontaneous ovulation, hirsutism, or acne. Statins reduce total and LDL cholesterol but have no effect on HDL, C-reactive protein, fasting insulin, or homeostasis model assessment of insulin resistance in PCOS women, in contrast to the general population. There have been no long-term studies of statins on clinical cardiac outcomes in women with PCOS. Coronary calcification is more prevalent and more severe in PCOS than in controls. In women under 60 years of age undergoing coronary angiography, the presence of polycystic ovaries on sonography has been associated with more arterial segments with >50% stenosis, but the relationship between PCOS and actual cardiovascular events remains unclear. Therapies for PCOS are varied in their effects and targets and include both nonpharmacologic as well as pharmacologic approaches. Weight loss is the primary therapy in PCOS--reduction in weight of as little as 5% can restore regular menses and improve response to ovulation- inducing and fertility medications. Metformin in premenopausal PCOS women has been associated with a reduction in features of MetS. Clamp studies using ethinyl estradiol/drosperinone combination failed to reveal evidence of an increase in either peripheral or hepatic insulin resistance. Subjects with PCOS have a 1.5-times higher baseline risk of venous thromboembolic disease and a 3.7-fold greater effect with OCP use compared with non-PCOS subjects. There is currently no genetic test to screen for or diagnose PCOS, and there is no test to assist in the choice of treatment strategies. Persistent bleeding should always be investigated for pregnancy and/or uterine pathology--including transvaginal ultrasound exam and endometrial biopsy--in women with PCOS. PCOS women can have difficulty conceiving. Those who become pregnant are at risk for gestational diabetes (which should be evaluated and managed appropriately) and the microvascular complications of diabetes. Assessment of a woman with PCOS for infertility involves evaluating for preconceptional issues that may affect response to therapy or lead to adverse pregnancy outcomes and evaluating the couple for other common infertility issues that may affect the choice of therapy, such as a semen analysis. Women with PCOS have multiple factors that may lead to an elevated risk of pregnancy, including a high prevalence of IGT--a clear risk factor for gestational diabetes--and MetS with hypertension, which increases the risk for pre-eclampsia and placental abruption. Women should be screened and treated for hypertension and diabetes prior to attempting conception. Women should be counseled about weight loss prior to attempting conception, although there are limited clinical trial data demonstrating a benefit to this recommendation. Treatment for women with PCOS and anovulatory infertility should begin with an oral agent such as clomiphene citrate or letrozole, an aromatase inhibitor.

Talking About Type 2 Diabetes: Family Communication From the Perspective of At-Risk Relatives.

The purpose of this study was to describe type 2 diabetes (T2DM) communication and risk reduction recommendations from the perspective of family members at risk for T2DM based on family history. Semistructured qualitative interviews were conducted with 33 individuals with a first-degree relative with T2DM. Participants were recruited from the community and a previous pharmacogenetics study. Deductive and inductive codes were applied to the transcripts. Conversations with family members with and without T2DM focused on symptoms and disease management of the family member with T2DM. With at-risk relatives, conversations also focused on prevention. Lack of perceived relevance to family members without T2DM was a barrier to communication. Recommendations to facilitate communication included education of an at-risk family member to increase awareness of risk, followed by sharing of learned information with others. Efforts are needed to increase awareness and improve communication about T2DM risk factors, familial risk, and risk reduction behaviors within families with a family history of T2DM. Family members with and without T2DM should be encouraged to communicate with their relatives about T2DM and the risk to family members. Identification of family members who can facilitate communication, education, and modeling of healthy behaviors may increase awareness and motivate at-risk individuals to engage in risk-reducing behaviors.

TOX and CDKN2A/B Gene Polymorphisms Are Associated with Type 2 Diabetes in Han Chinese.

To study associations between type 2 diabetes (T2DM) candidate genes and microvascular complications of diabetes (MVCDs), we performed case-control association studies for both T2DM and MVCDs in Han Chinese subjects. We recruited 1,939 unrelated Han Chinese T2DM patients and 918 individuals with normal blood glucose levels as nondiabetic controls. Among T2DM patients, 1116 have MVCDs, 266 have a history of T2DM of >10 years but never developed MVCDs. Eighty-two single-nucleotide polymorphisms (SNPs) in 54 candidate genes were genotyped. Discrete association studies were performed by the PLINK program for T2DM and MVCDs. Significant associations were found among candidate gene SNPs and T2DM, including rs1526167 of the TOX gene (allele A, P = 2.85 × 10−9, OR = 1.44). The SNP rs10811661 of the CDKN2A/B gene was also associated with T2DM (allele T, P = 4.09 × 10−7, OR = 1.36). When we used control patients with >10 years of T2DM history without MVCD, we found that the G allele of SNP rs1526167 of the TOX gene was associated with MVCD (nominal P = 4.33 × 10−4). In our study, significant associations were found between TOX and CDKN2A/B gene SNPs and T2DM. The TOX polymorphism might account for the higher risk of T2DM and the lower risk of MVCDs in the Han Chinese population.

Lower HOMA-β values are detected among individuals with variant of E23K polymorphism of potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) gene

BackgroundType 2 Diabetes Mellitus (T2DM) is a multifactorial disease involving both genetic and also environmental factors. Potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) gene, an ATP-sensitive potassium channel-coding gene, contributes to insulin secretion. ObjectivesThis research aimed to investigate E23K polymorphism in KCNJ11 gene and insulin secretion in individuals with family history of T2DM (cases) and without family history of T2DM (controls). MethodThis research was a case-control study involving 34 cases and 34 controls. E23K polymorphism of KCNJ11 was detected with PCR-RFLP. All of the obtained data were statistically analyzed with T-test, Mann–Whitney U-test, Chi-Square and One-Way ANOVA. ResultFrequency of AA genotype in individuals with family history of T2DM (41%) was higher than in individuals without family history of T2DM (6%) (p=0.001). Frequency of A allele in individuals with family history of T2DM (68%) was higher than in individuals without family history of T2DM (38%) (p=0.001). The risk of A allele in individuals with family history of T2DM was 3 times higher than in individuals without family history of T2DM (p=0.001, OR 3.38, CI 95% 1.67–6.84). Homeostasis Model Assessment β (HOMA-β) values of AA genotype (85.44%±39.55) were lower than that of GA (212.20%±79.30) and GG (254.00%±61.98) genotypes (p=0.000). ConclusionThe risk of having A allele in individuals with family history of T2DM is higher than that in individuals without family history of T2DM. HOMA-β values of AA genotype are lower than that of GA and GG genotypes.

Association Between Major Depression and Type 2 Diabetes in Midlife

Cohort studies suggest that the relationship between major depression (MD) and Type 2 diabetes (T2DM) is bidirectional. However, this association may be confounded by shared genetic or environmental factors. The objective of this study was to use a twin design to investigate the association between MD and T2DM. Data come from the Screening Across the Lifespan Twin Study, a sample of monozygotic and dizygotic twins 40 years or older sampled from the Swedish Twin Registry (n = 37,043). MD was assessed by using the Composite International Diagnostic Inventory. Structural equation twin modeling and Cox proportional hazards modeling were used to assess the relationship between MD and T2DM. Approximately 19% of respondents had a history of MD and 5% had a history of T2DM. MD was associated with 32% increased likelihood of T2DM (95% confidence interval = 1.00-1.80) among twins aged 40 to 55 years, even after accounting for genetic risk, but was not associated with T2DM among twins older than 55 years. T2DM was associated with 33% increased likelihood of MD (95% confidence interval = 1.02-1.72) among younger, but not older twins. Cholesky decomposition twin modeling indicated that common unique environmental factors contribute to the association between MD and T2DM. Environmental factors that are unique to individuals (i.e., not shared within families) but common to both MD and T2DM contribute to their co-occurrence in midlife. However, we cannot exclude the possibility of bidirectional causation as an alternate explanation. It is likely that multiple processes are operating to effect the relation between psychiatric and medical conditions in midlife.

Associations of circulating 25(OH)D with cardiometabolic disorders underlying type 2 diabetes mellitus in an Aboriginal Canadian community

AimsTo investigate the associations of 25-hydroxyvitamin D (25(OH)D) with insulin resistance (IR), beta-cell function and metabolic syndrome (MetS) in a First Nations population. MethodsWe conducted a cross-sectional analysis using data from the Sandy Lake Health and Diabetes Project (2003–2005). A total of 390 participants (>12y) were assessed for 25(OH)D, fasting glucose, insulin, lipids, blood pressure, inflammatory markers, anthropometric and lifestyle variables and a 75-g oral glucose tolerance test was administered. IR was calculated using the Matsuda insulin sensitivity index (ISOGTT) and the computational homeostasis model assessment of IR (HOMA2-IR). Beta-cell function was calculated using the insulinogenic index (IGI) divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2). The 2009 harmonized criteria were used to define MetS. ResultsHigher 25(OH)D was associated with a decreased prevalence of dysglycemia (OR=0.71 95% CI, 0.51–0.97 per SD increase). In addition, there were significant associations of 25(OH)D with measures of insulin action (ISOGTT; beta=0.31; 95% CI, 0.12, 0.49; HOMA2-IR; beta=−29; 95% CI −0.46, −0.11 and beta-cell function (ISSI-2; beta=0.15; 95% CI, 0.02, 0.28). The prevalence of MetS was 41%. There was a decreased risk (OR=0.73, 95% CI 0.56, 0.94) of MetS per SD increase in baseline 25(OH)D. Finally, there was a significant positive association of 25(OH)D with adiponectin (beta=0.16; 95% CI=0.01, 0.31). ConclusionsThese results support a potential role for vitamin D metabolism in the natural history of T2DM among Aboriginal Canadians, although carefully designed randomized trials will be required to establish causality.

Comorbidities of Childhood Obesity

Obesity in urban children both in India and across the world, shows a rising trend and, hence it is necessary to continue surveillance. Obese children experience immediate health consequences and comorbities like metabolic syndrome- insulin resistance including hypertension, hyperinsulinemia, hyperlipidemia; pre diabetes, Type II diabetes (T2DM), polycystic ovary syndrome (PCOS), sleep apnea and asthma, joint inflammation, joint pain, back pain, skin changes like acanthosis nigricans, gastroesophageal reflux, non alcoholic fatty liver, dental problems and psychological problems. Cardiovascular complications include high blood pressure which may be associated with left ventricular hypertrophy and higher intima thickness of carotid arteries. Screening for lipids should start at around 8 years in high risk children (obese or with adverse family history etc). Asian Indians have higher prevalence of upper body visceral fat distribution, PCOS, higher insulin resistance family history of T2 DM. Obesity was significantly related to current asthma among children and adolescents. Obstructive sleep apnoea produces night time hypoxic episodes affecting children snoring, morning headache, daytime sleepiness with difficulty in learning and memory. Acne, skinfold fungal infection and hyperpigmentation including acanthosis nigricans are common manifestations and may be associated with PCOS. Obesity is also associated with Attention Deficit Hyperactive Disorder psychological disorders and depression. Sometimes complications may also present as medical emergencies in severe obesity. Early diagnosis and detailed knowledge of these comorbities lead to effective treatment and prevent complications in adulthood.

Insulin and BMI as predictors of adult type 2 diabetes mellitus.

Fasting insulin concentrations are increasingly being used as a surrogate for insulin resistance and risk for type 2 diabetes (T2DM), although associations with adult outcomes are unclear. Our objective was to determine whether fasting insulin concentrations in childhood associate with later T2DM. Fasting insulin values were available from 2478 participants in the longitudinal Cardiovascular Risk in Young Finns Study at baseline age 3 to 18 years, along with data on adult T2DM (N = 84, mean age = 39.6 years). Among 3- to 6-year-olds, a 1-SD increase in fasting insulin was associated with a relative risk (RR) of 2.04 (95% confidence interval [CI], 1.54-2.70) for later T2DM, which remained significant after we adjusted for BMI and parental history of T2DM. For those aged 9 to 18 years, a 1-SD increase in insulin was associated with an RR of 1.32 (95% CI, 1.06-1.65) for T2DM, but this became nonsignificant after we adjusted for BMI and parental history of T2DM. In the latter age group, a 1-SD increase in BMI was associated with an RR of 1.45 (95% CI, 1.21-1.73) for T2DM, with adjustment for insulin and parental history of T2DM not improving this association. BMI in younger children was not associated with later T2DM. In life course analyses, those with T2DM had higher fasting insulin levels in early childhood and later adulthood but not in peripubertal years. Elevated fasting insulin concentrations in early childhood, but not adolescence, are independently associated with an elevated risk of T2DM in adulthood.

Circulating human epidermal growth factor receptor 2 (HER2) is associated with hyperglycaemia and insulin resistance.

Type 2 diabetes mellitus (T2DM) and human epidermal growth factor receptor 2 (HER2) are associated with cancer, although the role of HER2 in T2DM is not well defined. The aim of this study was to investigate the association between HER2 levels and T2DM and whether that association differed in Swedish people born in Iraq or Sweden. Circulating HER2 levels were analyzed by the Luminex assay in 95 Iraqi-born and 75 Swedish-born Swedes. There were significant differences in HER2 among those with normal glucose tolerance (NGT), impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), and T2DM in the entire population after adjusting for age, sex, and body mass index (BMI; P = 0.03). Stratification of data according to country of birth revealed significant differences in HER2 levels among NGT, IFG/IGT, and T2DM groups only in Swedes (P = 0.007). For the entire study population, there was a positive association between HER2 and hyperglycemia (IFG and/or IGT + T2DM; P = 0.011), BMI, waist circumference, serum insulin, homeostatic model assessment of β-cell function, HbA1c, triglycerides, and C-peptide (P < 0.05), and a negative association between HER2 and insulin sensitivity index (ISI; P < 0.0001). Bivariate and multivariate linear regression analyses on the whole study population revealed that the associations between hyperglycemia and HER2, as well as between ISI and HER2, were independent of factors known to be associated with T2DM and insulin resistance (e.g. demographics, obesity, lipids, sedentary lifestyle, a family history of T2DM, C-peptide, and C-reactive protein). There is an independent association between HER2 levels and hyperglycemia and insulin resistance that is not modified by country of birth.