Janet B McGill

OBJECTIVE We evaluated whether adding basal insulin to metformin in adults with early type 2 diabetes mellitus (T2DM) would increase emotional distress relative to other treatments. RESEARCH DESIGN AND METHODS The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) of adults with T2DM of <10 years’ duration, HbA1c 6.8–8.5%, and taking metformin monotherapy randomly assigned participants to add insulin glargine U-100, sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or the dipeptidyl peptidase 4 inhibitor sitagliptin. The Emotional Distress Substudy enrolled 1,739 GRADE participants (mean [SD] age 58.0 [10.2] years, 32% female, 56% non-Hispanic White, 18% non-Hispanic Black, 17% Hispanic) and assessed diabetes distress and depressive symptoms every 6 months. Analyses examined …

Metabolic syndrome affects more than one in three adults and is associated with increased risk of diabetes, cardiovascular disease, and all-cause mortality. Muscle insulin resistance is a major contributor to the development of the metabolic syndrome. Studies in mice have linked skeletal muscle sarcoplasmic reticulum (SR) phospholipid composition to sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity and insulin sensitivity. To determine if the presence of metabolic syndrome alters specific phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species in human sarcoplasmic reticulum (SR), we compared SR phospholipid composition in skeletal muscle from sedentary subjects with metabolic syndrome and sedentary control subjects without metabolic syndrome. Both total PC and total PE were significantly decreased in skeletal muscle SR of sedentary metabolic syndrome patients compared to …

Background The role of glycemic control and its variability on the rate of kidney function decline after the onset of diabetic kidney disease (DKD) remains unclear. Methods The association between baseline glycated hemoglobin (HbA1c) and rates of estimated glomerular filtration rate (eGFR) loss during follow-up was examined by mixed-effects linear regression in 530 individuals with type 1 diabetes and early-to-moderate DKD from the Preventing Early Renal Loss (PERL) trial and 2378 individuals with type 2 diabetes and established DKD from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. The benefit of intensive vs standard glycemic control in slowing eGFR decline was examined in ACCORD. The associations between continuous glucose monitoring-derived short-term glycemic variability indices and rate of eGFR decline were also evaluated in …

OBJECTIVE To compare the long-term effects of glucose-lowering medications (insulin glargine U-100, glimepiride, liraglutide, sitagliptin) when added to metformin on insulin sensitivity and β-cell function. RESEARCH DESIGN AND METHODS In the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) cohort with type 2 diabetes (n = 4,801), HOMA2 was used to estimate insulin sensitivity (HOMA2-%S) and fasting β-cell function (HOMA2-%B) at baseline and 1, 3, and 5 years on treatment. Oral glucose tolerance test β-cell responses (C-peptide index [CPI] and total C-peptide response [incremental C-peptide/incremental glucose over 120 min]) were evaluated at the same time points. These responses adjusted for HOMA2-%S in regression analysis provided estimates of β-cell function. RESULTS HOMA2-%S increased …

Introduction Sodium glucose cotransporter (SGLT) inhibitors may increase beta-hydroxybutyrate (BHB) in insulin-requiring patients. We determined factors associated with BHB changes from baseline (ΔBHB) and diabetic ketoacidosis (DKA) in patients with type 1 diabetes (T1D) receiving sotagliflozin as an insulin adjunct. Research Design and Methods This post-hoc analysis compared ΔBHB levels in adults with T1D receiving sotagliflozin 400 mg or placebo for 6 months. We evaluated clinical and metabolic factors associated with ΔBHB and used logistic regression models to determine predictors associated with BHB values >0.6 and >1.5 mmol/L (inTandem3 population; N=1402) or with DKA events in a pooled analysis (inTandem1-3; N=2453). Results From baseline (median, 0.13 mmol/L), median fasting BHB increased by 0.04 mmol/L (95% confidence interval, 0.03–0.05; P<0.001) at 24 weeks with …

This case highlights the importance of suspecting MODY, and specifically HNF1b defects, when patients present with this constellation of findings. 3 Diagnostic workup includes antibody and C-peptide testing, followed by molecular genetic testing. Establishing a MODY diagnosis is important as therapeutic strategies, transplant counseling, and routine health maintenance screenings vary by genetic mutation and mechanism of disease. Inheritance is generally autosomal dominant, which is important for genetic and reproductive counseling and may prompt genetic testing in family members.

AimsDespite guideline-recommended treatments, including renin angiotensin system inhibition, up to 40 % of individuals with type 1 diabetes develop chronic kidney disease (CKD) putting them at risk of kidney failure. Finerenone is approved to reduce the risk of kidney failure in individuals with type 2 diabetes. We postulate that finerenone will demonstrate benefits on kidney outcomes in people with type 1 diabetes.MethodsFINE-ONE (NCT05901831) is a randomised, placebo-controlled, double-blind phase III trial of 7.5 months’ duration in ∼220 adults with type 1 diabetes, urine albumin/creatinine ratio (UACR) of ≥ 200–< 5000 mg/g (≥ 22.6–< 565 mg/mmol) and eGFR of ≥ 25–< 90 ml/min/1.73 m2.ResultsThe primary endpoint is relative change in UACR from baseline over 6 months. UACR is used as a bridging biomarker (BB), since the treatment effect of finerenone on UACR was associated with its efficacy …

People with type 2 diabetes (T2DM) and those with prediabetes have an increased risk of heart failure (HF). Longer duration of T2DM correlates with a greater risk of HF, but HF is also seen in patients with recent‐onset diabetes. Insulin resistance is more likely to be present in patients with HF. The risk of HF persists even in the face of standard‐of‐care preventive treatments for atherosclerotic cardiovascular (CV) disease. HF is commonly the presenting symptom of CV disease in people with diabetes and is the most expensive complication of diabetes because of the high cost of hospitalizations. Recently hospitalization for HF has been included in CV outcome trials (CVOTs), including for medications that are used to treat T2DM, which has led to new therapies for all HF patients. In addition, these CVOTs have shown that many drugs used in the therapy of diabetes are either neutral or detrimental in the HF patient …

For the few reports in the literature, this case is done with clinical and epidemiological diagnostic of the hemorrhagic chickenpox which was treated with antiviral, immunoglobulins and antibiotics (for over infection), with positive evolution. Chickenpox is a virus primary infection VZV (varicella-zoster) that generates a febrile illness accompanied by a generalized rash. Epidemic form occurs mainly in children aged from 2 to 10 years, it is transmitted by drops that come from the nasopharynx, with a benign course. If there is immune deficiency, the clinical form of hemorrhagic varicella can occur with an unfavorable outcome.

Rationale and Design of a Phase 3 Registration Trial Investigating Finerenone in Participants with CKD and Type 1 Diabetes Using a Urine Albumin-Creatinine Ratio (UACR) End Point (FINE-ONE) — The Capital Region of Denmark's Research Portal Skip to main navigation Skip to search Skip to main content The Capital Region of Denmark's Research Portal Home The Capital Region of Denmark's Research Portal Logo Help & FAQ Dansk English Home Hospitals/departments Researchers Research output Activities Prizes Search by expertise, name or affiliation Rationale and Design of a Phase 3 Registration Trial Investigating Finerenone in Participants with CKD and Type 1 Diabetes Using a Urine Albumin-Creatinine Ratio (UACR) End Point (FINE-ONE) Hiddo J Lambers Heerspink, Peter Rossing, Per-Henrik Groop, Helen M Colhoun, Robert Lawatscheck, Charlie Scott, Janet B McGill Steno Diabetes Center …

This month’s issue of ACCR highlights interesting diabetes cases with diagnostic and management challenges. You will find a summary of the cases in this issue with key points and learnings below. For more details, please access ACCR online journal available at https://www. aaceclinicalcasereports. com/.Diagnostic conundrums are illustrated by cases of monogenic diabetes that were initially diagnosed as either type 1 or type 2 diabetes. Kumar and colleagues present a case of a young woman whose monogenic diabetes was diagnosed after a pathogenic∼ 1.8 Mb loss of 17q12 was found on chromosomal microarray of her serous ovarian carcinoma, identifying a disease association not previously reported.

Numerous studies have demonstrated the clinical benefits of continuous glucose monitoring (CGM) in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) who are treated with intensive insulin regimens. Based on this evidence, CGM is now a standard of care for individuals within these diabetes populations and widely covered by commercial and public insurers. Moreover, recent clinical guidelines from the American Diabetes Association and American Association of Clinical Endocrinology now endorse CGM use in individuals treated with nonintensive insulin regimens. However, despite increasing evidence supporting CGM use for individuals treated with less-intensive insulin therapy or noninsulin medications, insurance coverage is limited or nonexistent. This narrative review reports key findings from recent randomized, observational, and retrospective studies investigating use of CGM in T2D …

Aim To evaluate the effect of finerenone by baseline HbA1c, HbA1c variability, diabetes duration and baseline insulin use on cardiorenal outcomes and diabetes progression. Materials and Methods Composite efficacy outcomes included cardiovascular (cardiovascular death, non‐fatal myocardial infarction, non‐fatal stroke or hospitalization for heart failure), kidney (kidney failure, sustained ≥ 57% estimated glomerular filtration rate decline or renal death) and diabetes progression (new insulin initiation, increase in antidiabetic medication, 1.0% increase in HbA1c from baseline, new diabetic ketoacidosis diagnosis or uncontrolled diabetes). Results In 13 026 participants, risk reductions in the cardiovascular and kidney composite outcomes with finerenone versus placebo were consistent across HbA1c quartiles (P interaction .52 and .09, respectively), HbA1c variability (P interaction .48 and .10), diabetes …

Background: The relationship of mean glucose measured with continuous glucose monitoring (CGM) and hemoglobin A1c (HbA1c) shows considerable variability between individuals with diabetes and may be influenced by race-related factors. Whether the relationship of mean glucose with HbA1c varies according to type 1 diabetes (T1D) or type 2 diabetes (T2D) has not been well evaluated. Methods: Data from 343 participants in four clinical trials (191 with T1D and 152 with T2D) were analyzed. Least squares linear regression models were fit with HbA1c as the dependent variable and mean glucose as the independent variable. Results: Mean age was 57 ± 15 years in the T1D cohort and 58 ± 10 years in the T2D cohort. The T1D cohort was 89% White non-Hispanic, 5% African American, 3% Hispanic, and 3% other or mixed race compared with 52%, 16%, 22%, and 9%, respectively, in the T2D cohort. The …

ImportanceType 2 diabetes (T2D) is the leading cause of kidney disease in the US. It is not known whether glucose-lowering medications differentially affect kidney function.ObjectiveTo evaluate kidney outcomes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) trial comparing 4 classes of glucose-lowering medications added to metformin for glycemic management in individuals with T2D.Design, Setting, and ParticipantsA randomized clinical trial was conducted at 36 sites across the US. Participants included adults with T2D for less than 10 years, a hemoglobin A1clevel between 6.8% and 8.5%, and estimated glomerular filtration rate (eGFR) greater than or equal to 60 mL/min/1.73 m2who were receiving metformin treatment. A total of 5047 participants were enrolled between July 8, 2013, and August 11, 2017, and followed up for a mean of 5.0 years (range, 0-7.6 years …

Objective: To evaluate safety and effectiveness of MiniMed™ 670G hybrid closed loop (HCL) in comparison with continuous subcutaneous insulin infusion (CSII) therapy for 6 months in persons with type 1 diabetes (T1D). Methods: Adults (aged 18–80 years), adolescents, and children (aged 2–17 years) with T1D who were using CSII therapy were enrolled and randomized (1:1) to 6 months of HCL intervention (n = 151, mean age of 39.9 ± 19.8 years) or CSII without continuous glucose monitoring (n = 151, 35.7 ± 18.4 years). Primary effectiveness endpoints included change in A1C for Group 1 (baseline A1C >8.0%), from baseline to the end of study, and difference in the end of study percentage of time spent below 70 mg/dL (%TBR <70 mg/dL) for Group 2 (baseline A1C ≤8.0%), to show superiority of HCL intervention versus control. Secondary effectiveness endpoints were change in A1C and %TBR …

Patients with type 2 diabetes are at an increased risk of developing heart failure and chronic kidney disease. The presence of these co‐morbidities substantially increases the risk of morbidity as well as mortality in patients with diabetes. The clinical focus has historically centred around reducing the risk of cardiovascular disease by targeting hyperglycaemia, hyperlipidaemia and hypertension. Nonetheless, patients with type 2 diabetes who have well‐controlled blood glucose, blood pressure and lipid levels may still go on to develop heart failure, kidney disease or both. Major diabetes and cardiovascular societies are now recommending the use of treatments such as sodium‐glucose co‐transporter‐2 inhibitors and non‐steroidal mineralocorticoid receptor antagonists, in addition to currently recommended therapies, to promote cardiorenal protection through alternative pathways as early as possible in individuals …

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Thus, there is an urgent need for safe and effective novel therapies. PDAC’s excessive reliance on glucose metabolism for its metabolic needs provides a target for metabolic therapy. Preclinical PDAC models have demonstrated that targeting the sodium-glucose co-transporter-2 (SGLT2) with dapagliflozin may be a novel strategy. Whether dapagliflozin is safe and efficacious in humans with PDAC is unclear.MethodsWe performed a phase 1b observational study (ClinicalTrials.gov ID NCT04542291; registered 09/09/2020) to test the safety and tolerability of dapagliflozin (5 mg p.o./day × 2 weeks escalated to 10 mg p.o./day × 6 weeks) added to standard Gemcitabine and nab-Paclitaxel (GnP) chemotherapy in patients with locally advanced and/or metastatic PDAC. Markers of efficacy including Response Evaluation Criteria in Solid …

Background Chronic kidney disease (CKD) is a complication of type 2 diabetes (T2D) with high morbidity and mortality. The prevalence of CKD in T2D is increasing due to rising numbers of persons with T2D. Multiple clinical trials have been conducted testing novel therapies to reduce the progression of CKD, cardiovascular morbidity, in particular hospitalization for heart failure, and mortality. Results of these clinical trials have informed guidelines for the management of CKD in T2D. Methods The epidemiology of CKD in T2D and the process of guideline writing, including data gathering, grading and consensus development, were reviewed. Recent guidelines for the management of CKD in T2D that include recent renal outcome clinical trials are reported, along with supporting evidence. Results All current guidelines recommend annual screening for CKD …

Background/ObjectiveMaturity-onset diabetes of the young type 5 (MODY5) is caused by a hepatocyte nuclear factor 1β (HNF1β) gene mutation on chromosome 17q12. HNF1β mutations have also been found in ovarian clear cell carcinoma, whereas ovarian non–clear cell carcinoma expresses this mutation rarely. 17q12 recurrent deletion syndrome features include MODY5, urogenital anomalies, and psychiatric and neurodevelopmental disorders. This is a report of a patient with 17q12 recurrent deletion syndrome with MODY5, uterine abnormalities, and low-grade serous ovarian cancer.Case ReportA 25-year-old woman with recently diagnosed stage IIIC low-grade serous ovarian carcinoma was evaluated at the endocrinology clinic for diabetes, which was diagnosed at the age of 12 years. C-peptide level was detectable and T1DM antibodies were negative. The mother had diabetes, partially septated uterus …