History Of Diabetes Mellitus Type Research Articles

Serum immunoglobulin concentrations and risk of type 2 diabetes mellitus in adults: a prospective cohort study from the TCLSIH study

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion and/or insulin action. Increasing evidence suggests that inflammation played an important role in the pathogenesis of T2DM. Prospective studies on the link between immunoglobulins concentrations and the risk of T2DM in adults are limited. We developed a cohort study including 7,093 adults without T2DM history. The incidence of T2DM was 16.45 per 1,000 person-years. Compared with the lowest quartiles, the hazard ratios (95% confidence intervals) of T2DM for the highest quartiles of IgG, IgE, IgM and IgA were 0.64 (0.48–0.85), 0.94 (0.72–1.23), 0.68 (0.50–0.92) and 1.62 (1.24–2.11) (P for trend was < 0.01, 0.84, 0.02 and < 0.0001), respectively, suggesting that serum IgG and IgM concentrations were inversely associated with the incidence of T2DM, and IgA levels were positively associated with the risk of T2DM in a general adult population.

Obstructive sleep apnea risk among adults with type 2 diabetes mellitus in an urban primary care setting of Mangalore, India

ABSTRACT Background: Obstructive sleep apnea (OSA) is an under-evaluated and under-treated problem, particularly among individuals with type 2 diabetes mellitus (T2DM). Therefore, in this study, we aim to determine the risk of OSA among adults with T2DM residing in an urban area of Mangalore and to elucidate the determinants of OSA among the study participants. Materials and Methods: A cross-sectional study was conducted for a period of 2 months among adult patients (≥ 18 years) with T2DM seeking health care at a primary care setting located in an urban area of Mangalore. Face-to-face interviews were conducted using a semi-structured proforma. STOP-BANG questionnaire was used to assess the risk of OSA among the study participants. The measurements, such as height, weight, and neck circumference, were conducted using standard techniques Results: The mean age of the study participants was 58.12 ± 11.60 years. The majority, (58.30%), were males, and 45.0% reported a family history of T2DM. A total of 108 (60.0%) experienced loud snoring while asleep, while 149 (82.80%) experienced tiredness during daytime. The mean body mass index (BMI) was 24.64 ± 4.9 kg/m2, while a neck circumference of &gt;40 cms was found in 28.90%. A total of 69 (38.30%) had a high risk of OSA with a STOP-BANG score ranging from 5 to 8, while 71 (39.40%) had a score ranging from 3 to 4 (intermediate risk). The statistically significant associations were found between age &gt;50 years, male gender, and diabetes for ≥ 7 years and high risk of OSA (P &lt; 0.001). Conclusion: More than a third of the study participants had a high risk of OSA. Age &gt; 50 years, male gender, and diabetes for ≥7 years were the factors associated with OSA.

Inter-relation between diabetes mellitus and hypertension in terms of incidence and prediction in Saudi Arabia: a retrospective cohort study

BackgroundHypertension (HTN) and type 2 diabetes mellitus (T2DM) are interconnected metabolic disorders with escalating global incidence and prevalence. However, no longitudinal studies have specifically examined the incidence of HTN and T2DM in the same study population. This study aimed to elucidate the association between HTN and T2DM and ascertain their respective roles in the development of each other.MethodsThis retrospective cohort study encompassed 809 Saudi patients from primary healthcare centers in Al Madinah Al Munawarah, Saudi Arabia. The sample was stratified into three cohorts: 226 patients with HTN but without T2DM, 274 patients with T2DM but without HTN, and 309 patients devoid of both T2DM and HTN. Over a retrospective follow-up period of approximately 5 years, incidence density rates (IDR) were computed for HTN in the T2DM cohort, T2DM in the HTN cohort, and both HTN and T2DM in the control cohort. Multiple logistic regression analysis was employed to identify predictors of HTN and T2DM.ResultsThe IDR of T2DM among patients with HTN stood at 73.9 (95% confidence interval [CI] 56, 92) per 1000 person-years, in contrast to 33.9 (95% CI 24, 44) per 1000 person-years in the control cohort (adjusted odds ratio [OR] = 7.1, 95%CI 3.55, 14.13). Conversely, the IDR of HTN among patients with type-2 T2DM was 55.9 (95% CI 42, 70) per 1000 person-years, while in the control cohort, it was 20.8 (95% CI 13, 28) per 1000 person-years (adjusted OR = 5.8, 95% CI 3.11, 11.09). Significant predictors of HTN in the logistic regression model encompassed age, smoking status, family history of HTN, T2DM status, and body mass index (BMI). Similarly, significant predictors of T2DM in the logistic regression model included age, sex, family history of T2DM, HTN, and BMI.ConclusionThis study unveils HTN and T2DM as mutually significant risk factors. The IDR of each condition in the presence of the other significantly exceeded that among individuals devoid of HTN or T2DM.

Positive parental history of diabetes is associated with early diagnosis, better dietary compliance, and glycemic control among type 2 diabetes patients in southern Sri Lanka

BackgroundParental history of diabetes is an established risk factor for type 2 diabetes mellitus (T2DM). There is limited data on the association of parental history with the prevalence of T2DM in Sri Lanka. The study aims to examine the prevalence and correlation of parental history and factors such as the onset age, glycaemic control, and self-reported dietary compliance among T2DM patients. With a rising incidence of T2DM in Sri Lanka, understanding the impact of parental history on age at diagnosis and glycemic control can aid in targeted screening and interventions.MethodsA cross-sectional study was carried out on 500 T2DM patients attending a diabetes clinic in Galle, the capital of Southern Sri Lanka with a multiethnic population. Convenient sampling strategy was followed in the recruitment process and a questionnaire-based method was used to collect the data. All the collected data was analysed using SPSS V 25.0.Results51.2% had a parental history of T2DM, and those with a positive parental history were diagnosed six years earlier than those with a negative parental history (p < 0.001). A significant correlation between parental history and gestational diabetes mellitus (GDM) was observed (p < 0.001). Patients with a parental history reported better dietary adherence (p < 0.001). Binary logistic regression analysis revealed patients with positive parental history had significantly lower HbA1C (p = 0.003, OR = 0.748).ConclusionT2DM patients with a parental history showed significant association with early diabetes onset, GDM, better glycemic control, and dietary adherence.

SOCIODEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF NEWLY DIAGNOSED TYPE 2 DIABETICS —A CROSS-SECTIONAL STUDY

Background: Five-hundred-thirty-six million adults are living with diabetes worldwide, 33 million in Pakistan ranking 3rd in position globally. We aimed to see the sociodemographic, baseline clinical and metabolic profile of newly diagnosed patients of Type 2 Diabetes Mellitus (T2DM). Methods: Sociodemographic data of 98 patients aged ?18 years presenting to Endocrinology Department of CDA Hospital Islamabad was collected on a self-developed questionnaire. The inclusion criteria were newly diagnosed T2DM patients, seeking medical advice to initiate therapy. Baseline clinical and metabolic profiles were recorded. Patients already on therapy were excluded. The data was analysed using SPSS-25. Results: Mean age of the patients was 48.92±12.46 years with female predominance (54, 55.1%). Mean Body Mass Index (BMI) was 29.15±4.99 Kg/m2, waist circumference 102.69±10.19 Cm, and HbA1c was 9.62±2.19%. Eighty-one (82.7%) patients belonged to families with monthly income PKR 30,000–40,000 (lower socio-economic status), 59 patients had &lt;7 years of schooling (60.2%), 51 patients had a negative family history of T2DM (52%), 79 patients were diagnosed within the last 6 months (80.6%), and 44 patients did not have co-morbidities (44.9%). Osmotic symptoms were present in 77 (77.8%) of patients at presentation. Complications of T2DM were present in 18 (18.4%) patients at baseline. Conclusion: T2DM is more prevalent in middle aged, overweight, female patients belonging to low socioeconomic status and have osmotic symptoms as main presenting complaint, HbA1c of 9.62%, and 52% patients had a negative family history of T2DM. The complications of T2DM were seen only in 18% at presentation. Pak J Physiol 2024;20(2):19-23

Impact of distress on the nutritional status of patients with type 2 diabetes mellitus at the National Hospital of Endocrinology in 2022

Diabetes Mellitus (DM), particularly Type 2 Diabetes Mellitus (T2DM), is one of the most prevalent non-communicable chronic diseases and poses significant challenges for the healthcare sector and the community. Distress in patients with T2DM leads to severe physical and mental consequences. This study aims to analyze the relationship between distress and the nutritional status of T2DM patients. A cross-sectional descriptive study was conducted on 203 T2DM patients at the National Hospital of Endocrinology from October to December 2022. Of the participants, 54.2 % were female with an average age of 62.1 (±12.4). The waist circumference (WC) and waist-to-hip ratio (WHR) were significantly different between genders (p < 0.05). The prevalence of overweight/obesity was high at 46.7 %, with females having a 2.3 times higher WC and a 1.5 times higher WHR compared to males. The study identified several factors related to the nutritional status and distress in T2DM patients, including age, gender, residence, family history of T2DM, lifestyle habits, and nutritional status (p < 0.05). Early and comprehensive evaluation of T2DM patients is essential to improve treatment outcomes and quality of life.

Vericiguat and Cardiovascular Outcomesin HeartFailure by Baseline Diabetes Status: Insights From the VICTORIA Trial.

Type 2 diabetes mellitus (T2DM) significantly worsens heart failure (HF) prognosis. This study sought to investigate the impact of T2DM on outcomes in patients enrolled in VICTORIA and assess the efficacy of vericiguat in patients with and without T2DM. Patients with HF with reduced ejection fraction were randomized to receive vericiguat or placebo in addition to standard therapy. The primary outcome was a composite of cardiovascular death or first heart failure hospitalization (HFH). A Cox proportional hazards model was used to calculate HRs and 95%CIs to assess if the effect of vericiguat differed by history of T2DM. Of 5,050 patients enrolled, 3,683 (72.9%) had glycosylated hemoglobin (HbA1c) measured at baseline. Of these, 2,270 (61.6%) had T2DM, 741 (20.1%) had pre-T2DM, 449 (12.2%) did not have T2DM, and 178 (4.8%) had undiagnosed T2DM. The risks of the primary outcome, HFH, and all-cause and cardiovascular mortality were high across all categories. The efficacy of vericiguat on the primary outcome did not differ in patients stratified by T2DM by history (HR: 0.92; 95%CI: 0.81-1.04), T2DM measured by HbA1c (HR: 0.77; 95%CI: 0.49-1.20), and pre-T2DM measured by HbA1c (HR: 0.88; 95%CI: 0.68-1.13) and in those with normoglycemia (HR: 1.02: 95%CI: 0.75-1.39; P for interaction=0.752). No significant differences were observed in subgroups with respect to the efficacy of vericiguat on HFH and all-cause or cardiovascular death. In this post hoc analysis of VICTORIA, vericiguat compared with placebo significantly reduced the risk of cardiovascular death or HFH in patients with worsening HF with reduced ejection fraction regardless of T2DM status. (A Study of Vericiguat in Participants With HeartFailure With Reduced Ejection Fraction [HFrEF] [Mk-1242-001] [VICTORIA]; NCT02861534).

Metformin-Insulin Combination Therapy Ameliorates Hyperglycemia in a COVID-19 Type-1 Diabetic Child with Insulin Resistance: A Case Report

Introduction: Recent studies have indicated that COVID-19 may be linked with type 1 diabetes mellitus (T1DM) in children. It has been observed that not only is there a potential risk of new-onset pediatric T1DM associated with COVID-19, but numerous cases also present with insulin resistance, necessitating prompt management. Case Presentation: We report the case of a 9-year-old girl with a history of T1DM who was admitted with hyperglycemia (blood sugar &gt; 750 mg/dL) and subsequently diagnosed with COVID-19. The co-administration of metformin and intravenous insulin successfully resolved subcutaneous insulin resistance, allowing the patient to be discharged in good health. Conclusions: Insulin resistance is a recognized complication of SARS-CoV-2 infection, and metformin combined with intravenous insulin has proven effective in managing hyperglycemia and improving insulin resistance in this context. Further research is necessary to elucidate the underlying mechanisms and develop optimal therapeutic strategies.

Exploring the Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Genitourinary Toxicities in Prostate Cancer Patients Undergoing Radiation Therapy: A Case Study and Discussion

Radiation therapy is a common treatment modality offered to patients with localized prostate cancer. It can be associated with early radiation-induced toxicities including dysuria, nocturia, frequency, urgency, spasm, and, rarely, hematuria. Early toxicities usually resolve once the treatment period has ended. Chronic toxicities are less common, and rarely, patients may experience radiation-induced hemorrhagic cystitis and hematuria months or years after radiation. We herein describe the case of a 65-year-old man with a past medical history of type-2 diabetes mellitus who experienced hemorrhagic cystitis for months following his radiation therapy. The patient was on sodium-glucose cotransporter-2 inhibitor therapy (empagliflozin), which we highlight as a potential risk factor for hemorrhagic cystitis. After cessation of Jardiance and initiation of semaglutide (GLP-1 agonist), his urinary symptoms significantly improved. To the best of our knowledge, this is the first such case reported.

Comparison of Pre-eclampsia Screening Algorithms in the First Trimester of Pregnancy Being Used in Thai Nguyen Province.

Objective To compare the rates of pregnancies in high-risk groups for preeclampsia recommended for aspirin prophylactic when screened using various common algorithms. Methods This cross-sectional study was conducted on 1726 pregnant women from 11 to 13 weeks six days of gestation receiving antenatal care at two hospitals: Thai Nguyen National Hospital and a hospital in Thai Nguyen Province from October 2022 to October 2023. All participants provided consent for the study. We collected maternal characteristics, obstetric history,mean arterial pressure (MAP), mean uterine artery-PI (UtA-PI), and placental growth factor serum (PLGF). Screening performance estimates were calculated using the Fetal Medicine Foundation (FMF) and National Institute for Health and Care Excellence (NICE) guidelines. All pregnant women in the study had their preeclampsia risk assessed using all three algorithms with two cut-off points.Our data was collected, entered and analyzed using SPSS software 20.0 (IBM Corp., Armonk, NY). Categorical data was reported as frequency and percentage. McNemar's test was used for analyzing differences in the sizes of individual groups. Results In our study, the most common high-risk factor identified was the history of preeclampsia, 132 cases (7.6%). According to the NICE guideline, BMI ≥ 35 (kg/m²) is considered a moderate risk factor for preeclampsia. Several risk factors, such as BMI ≥ 35 kg/m² and history of diabetes mellitus type 1, were not present in any participants. Only one pregnant woman had chronic kidney disease (0.06%). Out of the 1726 pregnant women surveyed, the rates of high-risk preeclampsia were as follows: 9.9% (171 cases) based on algorithm 1; 10.8% (187 cases) based on algorithm 2 with a cut-off point > 1/100, 11.8% (203 cases) with a cut-off point > 1/150; 10.3 % (178 cases) based on algorithm 3 with a cut-off point > 1/100, and 11.6% (201 cases) with a cut-off point > 1/150. Among these algorithms, pregnant women in the high-risk preeclampsia group were advised to consider taking low-dose aspirin. Conclusion Screening for pre-eclampsia based on NICE recommendations resulted in a lower number of high-risk pregnant women requiring prophylactic aspirin use compared to other algorithms. This means that some pregnant women at risk of developing preeclampsia are not recommended to use aspirin as a preventive measure. Adding PLGF to the screening strategy will help us get closer to pregnant women who are truly at risk of progressing to preterm preeclampsia.

Retatruide' drug trial: A paradigm shift in Type 2 Diabetes management.

Type 2 diabetes mellitus (T2DM) is a chronic medical condition characterised by persistent hyperglycemia caused by insulin resistance and impaired beta cell function. Typically, it occurs in individuals aged 45 and above, but due to the growing prevalence of obesity and sedentary lifestyle, it is increasingly being diagnosed in younger adults and adolescents. A positive family history of T2DM and specific genes such as TCF7L2 and PPARG also play an essential role.[1] Consequently, persistent hyperglycemia in type 2 DM can give rise to a range of microvascular complications such as retinopathy, neuropathy and nephropathy and macrovascular complications such as coronary artery and cerebrovascular diseases. T2DM accounts for 90% of the cases of diabetes, raising concern among the healthcare sector worldwide. In 2017, approximately 462 million individuals were affected by type 2 DM, accounting for 6.28% of the world’s population. By 2030, it is estimated that the global prevalence will rise to 7079 individuals per 100,000.[2] To prevent the complications caused by T2DM, it is essential to prioritize glycemic control. First and foremost, effective dietary control is pivotal. It has been established that obesity in individuals with T2DM is closely associated with insulin resistance and defects in insulin secretions thus managing the calorie intake is mandatory. However, pharmacologic intervention with oral glucose-lowering agents or insulin therapy is necessary when the patient’s blood glucose doesn’t fall within normal limits despite weight reduction, exercise and dietary modifications. The first line pharmacological agent used is Metformin, an oral medication that reduces glucose production in the liver. Additionally, insulin secretagogues such as sulfonylureas and glinides promote insulin release by stimulating beta cells. Thiazolidinediones is another example of an oral agent used to treat diabetes by enhancing glucose uptake by the muscle, liver and adipose tissue.[3] Furthermore, it is crucial to understand that the Incretin effect, responsible for stimulating insulin secretion after meals, is primarily mediated by gut-derived incretin hormones known as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). However, patients with type 2 diabetes (T2DM) commonly exhibit defects in this process. To address this issue, in addition to oral medications, injectable drugs such as RA-GLP1 (Semaglutide, Dulaglutide) are administered to emulate the actions of human GLP-1 effectively. These injectable treatments are vital in reducing postprandial hyperglycemia and have become indispensable in managing T2DM. ---Continue

Unveiling osteoporosis in type 2 diabetes: A diagnostic and therapeutic challenge

This case report explores the complex relationship between Type 2 Diabetes Mellitus (T2DM) and osteoporosis, highlighting the diagnostic and therapeutic challenges encountered. It presents the journey of P.M, a 55-year-old woman with a 10-year history of T2DM, who was initially screened for osteopenia with MOC DEXA, which failed to accurately diagnose her condition. Subsequent dorsolumbar radiography revealed significant osteoporosis, leading to an integrated treatment approach with denosumab, lifestyle changes, and careful diabetes management. The case highlights the limitations of traditional diagnostic methods in diabetic patients and underscores the need for personalized, comprehensive care strategies to address both diabetes and osteoporosis, illustrating the potential for improved outcomes through targeted therapies and ongoing patient monitoring. This report contributes to a broader understanding of the management of complex comorbid conditions and underscores the need for continued innovation in clinical practice.

Gestational diabetes mellitus as a risk factor for future Type-2 diabetes mellitus: An experience from a tertiary care diabetes hospital, Karachi - Pakistan.

To evaluate the history of gestational diabetes mellitus and other risk factors in women presenting with Type-2 diabetes mellitus at a tertiary care hospital. This cross-sectional study was carried out at Baqai Institute of Diabetology & Endocrinology (BIDE), Baqai Medical University (BMU), Karachi-Pakistan from July 2019 to May 2022. Women with Type-2 diabetes mellitus (T2DM) visiting outpatient department of BIDE with a previous history of GDM were recruited. Details were obtained on pre-designed questionnaire after taking informed written consent. A total of 378 women who had a prior history of GDM were included. Mean age (years) was 43.53±10.17. Mostly women were obese (BMI = 30.53±6.08) and have sedentary lifestyle. Mean HbA1c (%) was 9.08±2.24. This study found family history of T2DM and hypertension were common risk factors in women with GDM history. Mostly, women were diagnosed as GDM during 2nd trimester 153(42%) and was mainly seen in multiparous women (occur in 4th and above pregnancy). We found hypertension as common complication during pregnancy. Around 46% women developed T2DM within one year of GDM diagnosis, and 29.6% between one to five years. Majority of women with GDM developed T2DM within five years of diagnosis. The potential associated risk factors were age, family history of diabetes, insulin use during pregnancy, trimester of GDM diagnosis, and hypertension during pregnancy. Awareness and life style modifications along with regular post-partum follow up with screening for T2DM should be part of GDM management to prevent or delay the occurrence of this serious complication.

Frequency of Type 2 Diabetes Mellitus among Patients with Hepatitis C Virus Infection

Background: Hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM) have established themselves as significant global health concerns, with a notable co-prevalence that suggests a potential pathophysiological connection. The increasing incidence of T2DM, particularly in developing countries, alongside the significant burden of HCV, poses challenges for healthcare systems and necessitates deeper understanding of their interrelation. Objective: This study aimed to ascertain the frequency of T2DM among patients with HCV infection and to investigate the potential association between HCV reactivity and the incidence of T2DM. Methods: A cross-sectional analysis was conducted at a molecular pathology laboratory in Lahore, Pakistan. Patients aged 18-60 years without cirrhosis or pre-existing T2DM were consecutively enrolled over a six-month period. Exclusion criteria included liver cancer, interferon therapy, end-stage renal disease, other viral hepatitides, and pregnancy. Data were collected via questionnaires after informed consent, with serum and hemoglobin A1c (HbA1c) levels measured. HCV reactivity was confirmed via real-time polymerase chain reaction (RT-PCR), and the frequency of T2DM was assessed by HbA1c criteria. Statistical analysis involved univariate analysis using SPSS version 25.0. Results: Among the 300 HCV-reactive patients, the frequency of T2DM was found to be 49.33% (148 patients). The mean age of participants was 42.71 ± 6.808 years, with 53.0% males and 47.0% females. Urban and rural participants were nearly equally represented. A significant association was noted between HCV reactivity and T2DM (p=0.001), while no significant relationship was found with gender, residence, marital status, or family history of T2DM. Conclusion: The study highlights a substantial frequency of T2DM in HCV-reactive patients and a significant association between HCV infection and the development of T2DM. Regular HbA1c monitoring in HCV-reactive patients is recommended for the early identification and management of T2DM.

MANAGEMENT OF COATED TONGUE RESEMBLES PSEUDOMEMBRANOUS CANDIDIASIS IN A MULTIDRUG-THERAPY PATIENT

Introduction: Coated tongue or tongue coating is characterized by white deposit covering dorsum of the tongue. The thick-coated tongue almost resembles oral candidiasis. It is challenging to make the diagnosis and provide the proper treatment especially when supporting examination tools are unavailable. Objective: To discuss the diagnosis making and management of coated tongue with suspicion of pseudomembranous candidiasis with a lack of supporting examination tools. Case(s): A 61-year-old man was referred to the Oral Medicine Clinic for oral examination. No complaints of pain in the oral cavity. He had a history of type-2 diabetes mellitus, coronary heart disease (CHD), and pleuritis and was taking medication. During hospitalization, never cleaned his oral cavity. Case Management: Intraorally, white plaque covering almost the entire dorsum of the tongue, which could be scraped off on the anterior 1/3 but not on the posterior 2/3. The diagnosis was suspected coated tongue with oral candidiasis as the differential diagnosis. The treatments were compressing the tongue using gauze soaked in 3% hydrogen peroxide (H2O2) solution, scrapping off using a tongue scraper, then rinsing with water. The thick-coated tongue can be easily removed. He was also given 0,2% chlorhexidine gluconate (CHX) mouthwash as an antiseptic and petroleum jelly for dry lips. The tongue condition improved on 2nd day therapy after rinsing regularly using 0,2% CHX. Conclusion: Recognizing the signs, symptoms, and associated factors of Candida infection is important. Coated tongue which resembles pseudomembranous candidiasis was successfully treated using 3% H2O2 compresses, tongue scraping, and 0.2% CHX mouthwash. Keywords: Chlorhexidine gluconate, Coated tongue, Hydrogen peroxide, Infection, Oral candidiasis

Whole-exome sequencing in familial type 2 diabetes identifies an atypical missense variant in the RyR2 gene.

Genome-wide association studies have identified several hundred loci associated with type 2 diabetes mellitus (T2DM). Additionally, pathogenic variants in several genes are known to cause monogenic diabetes that overlaps clinically with T2DM. Whole-exome sequencing of related individuals with T2DM is a powerful approach to identify novel high-penetrance disease variants in coding regions of the genome. We performed whole-exome sequencing on four related individuals with T2DM - including one individual diagnosed at the age of 33 years. The individuals were negative for mutations in monogenic diabetes genes, had a strong family history of T2DM, and presented with several characteristics of metabolic syndrome. A missense variant (p.N2291D) in the type 2 ryanodine receptor (RyR2) gene was one of eight rare coding variants shared by all individuals. The variant was absent in large population databases and affects a highly conserved amino acid located in a mutational hotspot for pathogenic variants in Catecholaminergic polymorphic ventricular tachycardia (CPVT). Electrocardiogram data did not reveal any cardiac abnormalities except a lower-than-normal resting heart rate (< 60 bpm) in two individuals - a phenotype observed in CPVT individuals with RyR2 mutations. RyR2-mediated Ca2+ release contributes to glucose-mediated insulin secretion and pathogenic RyR2 mutations cause glucose intolerance in humans and mice. Analysis of glucose tolerance testing data revealed that missense mutations in a CPVT mutation hotspot region - overlapping the p.N2291D variant - are associated with complete penetrance for glucose intolerance. In conclusion, we have identified an atypical missense variant in the RyR2 gene that co-segregates with diabetes in the absence of overt CPVT.

Association between pregnancy-related complications and development of type 2 diabetes and hypertension in women: an umbrella review

BackgroundDespite many systematic reviews and meta-analyses examining the associations of pregnancy complications with risk of type 2 diabetes mellitus (T2DM) and hypertension, previous umbrella reviews have only examined a single pregnancy complication. Here we have synthesised evidence from systematic reviews and meta-analyses on the associations of a wide range of pregnancy-related complications with risk of developing T2DM and hypertension.MethodsMedline, Embase and Cochrane Database of Systematic Reviews were searched from inception until 26 September 2022 for systematic reviews and meta-analysis examining the association between pregnancy complications and risk of T2DM and hypertension. Screening of articles, data extraction and quality appraisal (AMSTAR2) were conducted independently by two reviewers using Covidence software. Data were extracted for studies that examined the risk of T2DM and hypertension in pregnant women with the pregnancy complication compared to pregnant women without the pregnancy complication. Summary estimates of each review were presented using tables, forest plots and narrative synthesis and reported following Preferred Reporting Items for Overviews of Reviews (PRIOR) guidelines.ResultsTen systematic reviews were included. Two pregnancy complications were identified. Gestational diabetes mellitus (GDM): One review showed GDM was associated with a 10-fold higher risk of T2DM at least 1 year after pregnancy (relative risk (RR) 9.51 (95% confidence interval (CI) 7.14 to 12.67) and although the association differed by ethnicity (white: RR 16.28 (95% CI 15.01 to 17.66), non-white: RR 10.38 (95% CI 4.61 to 23.39), mixed: RR 8.31 (95% CI 5.44 to 12.69)), the between subgroups difference were not statistically significant at 5% significance level. Another review showed GDM was associated with higher mean blood pressure at least 3 months postpartum (mean difference in systolic blood pressure: 2.57 (95% CI 1.74 to 3.40) mmHg and mean difference in diastolic blood pressure: 1.89 (95% CI 1.32 to 2.46) mmHg). Hypertensive disorders of pregnancy (HDP): Three reviews showed women with a history of HDP were 3 to 6 times more likely to develop hypertension at least 6 weeks after pregnancy compared to women without HDP (meta-analysis with largest number of studies: odds ratio (OR) 4.33 (3.51 to 5.33)) and one review reported a higher rate of T2DM after HDP (hazard ratio (HR) 2.24 (1.95 to 2.58)) at least a year after pregnancy. One of the three reviews and five other reviews reported women with a history of preeclampsia were 3 to 7 times more likely to develop hypertension at least 6 weeks postpartum (meta-analysis with the largest number of studies: OR 3.90 (3.16 to 4.82) with one of these reviews reporting the association was greatest in women from Asia (Asia: OR 7.54 (95% CI 2.49 to 22.81), Europe: OR 2.19 (95% CI 0.30 to 16.02), North and South America: OR 3.32 (95% CI 1.26 to 8.74)).ConclusionsGDM and HDP are associated with a greater risk of developing T2DM and hypertension. Common confounders adjusted for across the included studies in the reviews were maternal age, body mass index (BMI), socioeconomic status, smoking status, pre-pregnancy and current BMI, parity, family history of T2DM or cardiovascular disease, ethnicity, and time of delivery. Further research is needed to evaluate the value of embedding these pregnancy complications as part of assessment for future risk of T2DM and chronic hypertension.

Preoperative duration of type 2 diabetes mellitus and remission after Roux-en-Y gastric bypass: A single center long-term cohort study.

Roux-en-Y gastric bypass (RYGB) has demonstrated excellent glycemic control and type 2 diabetes mellitus (T2DM) remission for patients with obesity and T2DM. Duration of T2DM is a consistent negative predictor of remission after RYGB. However, the exact timing to offer surgical intervention during the course of the disease is not well elucidated. We performed a retrospective cohort study between 2008-2020 to establish the exact association between duration of T2DM and remission after RYGB. We divided our cohort into quartiles of preoperative disease duration to quantify the change in remission rates for each year of delay between T2DM diagnosis and RYGB. We also compared the average time to remission and changes in glycemic control parameters. A total of 519 patients (67.2% female; age 53.4±10.7y; BMI 46.6±8.4kg/m2) with a follow-up period of 6.6±3.8 years were included. Remission was demonstrated in 51% of patients. Longer duration of T2DM was a significant negative predictor of remission with an estimated decrease in remission rates of 7% for each year of delay ([OR=0.931 (95% CI 0.892-0.971)]; P<0.001). Compared to patients with <3 years of T2DM, remission decreased by 37% for patients with 3-6 years, 64% for those with 7-12 years and 81% for patients with more than 12 years (P<0.001). Half of the patients reached T2DM remission after 0.5 and 1.1 years respectively for the first and second quartiles, while patients in the other quartiles never reached 50% remission. Lastly, we noted an overall improvement in all glycemic control parameters for all quartiles at last follow-up. Patients with a recent history of T2DM who undergo early RYGB experience significantly higher and earlier T2DM remission compared to patients with a prolonged history of preoperative T2DM, suggesting potential benefit of early surgical intervention to manage patients with obesity and T2DM.

Association of Obesity With Type 2 Diabetes Mellitus: A Hospital-Based Unmatched Case-Control Study.

Background The prevalence of type 2 diabetes mellitus (T2DM) and obesity is alarmingly increasing with the accessibility of the modern lifestyle. This study aimed to assess the association of obesity with T2DM among the patients visiting the Medicine Department of Ayub Teaching Hospital, Abbottabad, Pakistan. Method This hospital-based, unmatched case-control study was conducted from March 2022 to September 2022. A total of 200 patients (age ≥ 18) (100 casesand 100 controls) were recruited. Those patients with a history of T2DM were selected as cases, and those without diabetes were selected as controls after taking informed written consent. Patients with BMI ≥ 25 were considered obese. Data were collected through a non-probability convenience sampling technique using a self-structured non-validated questionnaire. Data were organized and analyzed through IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY). Results We found a significant positive association of obesity with T2DM with a crude odds ratio of 3.6 (95% CI: 2.0-6.6), a p-value of 0.000, and an adjusted odd ratio of 3.7 (95% CI: 1.9 - 7.1), with a p-value of 0.004 (adjusted for potential confounders, including gender, age group, stress, and status of physical activeness) using a logistic regression model. Conclusion It is concluded that obesity is strongly associated with developing T2DMand lack of physical activity, people over 45 years, and males with obesity have a higher chance of developing T2DM.

Missed Opportunities in Type 2 Diabetes Mellitus: A Narrative Review.

Type 2 diabetes mellitus (T2DM) is a significant health problem around the world. This review aims to define missed opportunities and how they apply to patients with T2DM. This narrative review describes the natural history of T2DM and also describes where missed opportunities may arise. Missed opportunities may relate to prevention, early detection, diagnosis, and treatment of diabetes. The cornerstone of T2DM prevention is the control of modifiable risk factors and lifestyle changes to potentially prevent diabetes. Early detection of T2DM is important as it is a chronic condition that can progress rapidly if untreated. Missed opportunities related to the diagnosis of T2DM draw attention to the heterogeneous presentation of diabetes. The condition can be incidentally identified in asymptomatic patients, so all healthcare professionals should be aware of the disease. Furthermore, it is not unexpected that patients with atypical symptoms may have a delay in diagnosis. The treatment-related missed opportunities in T2DM are broad and include self-care, education, remission of T2DM, risk factor management, prevention of complications, medication therapy and compliance, as well as individualized care. Considering patient pathways is a useful approach to evaluate missed opportunities in patient care. Missed opportunities are a concept that is not often considered in diabetes care, which calls upon reflection of real-world activities and consideration of whether patient outcomes could have been improved with changes in decision-making. Future studies that aim to improve patient care should consider this concept.