Fluctuations in waist circumference increase diabetes risk: a 4-year cohort study in 61,587 older adults

Purpose To evaluate the effect of fluctuations in waist circumference (WC), weight, and body mass index (BMI) on the incidence of diabetes in older adults. Patients and methods A prospective cohort of 61,587 older adults (age, 60–96 years) who did not have diabetes at study initiation was examined. Data on weight, BMI, and WC were collected, and participants were followed up until 31 December 2018. The main end point was new-onset diabetes. A Cox regression model was used to estimate the risk of diabetes (hazard ratios [HRs] and confidence intervals [CI]) in these participants. Results During a mean follow-up of 3.6 years, being overweight (HR [95% CI] 1.87 [1.62–2.17]), obesity (1.41 [1.26–1.59]), abdominal obesity (1.42 [1.28–1.58]), and obesity plus abdominal obesity at baseline (1.93 [1.66–2.25]) increased the risk of diabetes onset. Compared with older adults who “maintained normal WC”, those who “remained abdominally obese” (HR = 1.66), “became abdominally obese” (HR = 1.58), or “achieved normal WC” (HR = 1.36) were at a higher risk of diabetes onset, as well as those with an increase in WC > 3 cm or > 5% compared with the baseline level. Weight gain or loss > 6 kg or weight gain > 5%, increase or decrease in BMI > 2 kg/m2, or an increase in BMI > 10% were associated with a higher diabetes risk. The diabetes risk was reduced by 19% in overweight older adults who exercised daily. Conclusion For older adults, WC, BMI, and healthy weight maintenance reduce the diabetes risk. The findings may provide evidence for developing guidelines of proper weight and WC control for older adults.

Transcriptomic Analysis of Patients With Clinical Suspicion of Maturity-onset Diabetes of the Young (MODY) With a Negative Genetic Diagnosis

BackgroundThe personalized management of each type of Mature-onset diabetes of the young (MODY), a non-autoimmune monogenic form of diabetes mellitus, achieves both avoiding invasive therapies and better defining the patient's prognosis and reducing future misdiagnoses by performing a screening family. Positive genetic diagnosis is achieved in only around 50% of patients with clinical characteristics of this disease, which leads us to propose in this study to evaluate the diagnostic utility of transcriptomic analysis in patients with clinical suspicion of MODY but a negative genetic diagnosis using Nanostring nCounter technology.ResultsWe conducted transcriptomic analysis of 19 MODY-associated genes in peripheral blood samples from 19 patients and 8 healthy controls. Normalized gene expression was compared between patients and controls and correlated with each patient’s biochemical and clinical variables. Z-scores were calculated to identify significant changes in gene expression in patients versus controls. Only 7 of the genes analyzed were detected in peripheral blood. HADH expression was significantly lower in patients versus controls. Among patients with suspected MODY, GLIS3 expression was higher in obese versus non-overweight patients, and in patients aged <25 versus >25 years at diabetes onset. Significant alteration with respect to controls of any gene was observed in 31.6% of patients. ConclusionsAlthough blood does not appear to be an adequate sample for transcriptomic analysis of patients with suspected MODY, it does allow identification of potential molecular targets causing the disease in a considerable proportion of cases.

Detecting insulitis in type 1 diabetes with ultrasound phase-change contrast agents

Type 1 diabetes (T1D) results from immune infiltration and destruction of insulin-producing β cells within the pancreatic islets of Langerhans (insulitis). Early diagnosis during presymptomatic T1D would allow for therapeutic intervention prior to substantial β-cell loss at onset. There are limited methods to track the progression of insulitis and β-cell mass decline. During insulitis, the islet microvasculature increases permeability, such that submicron-sized particles can extravasate and accumulate within the islet microenvironment. Ultrasound is a widely deployable and cost-effective clinical imaging modality. However, conventional microbubble contrast agents are restricted to the vasculature. Submicron nanodroplet (ND) phase-change agents can be vaporized into micron-sized bubbles, serving as a microbubble precursor. We tested whether NDs extravasate into the immune-infiltrated islet microenvironment. We performed ultrasound contrast-imaging following ND infusion in nonobese diabetic (NOD) mice and NOD;Rag1ko controls and tracked diabetes development. We measured the biodistribution of fluorescently labeled NDs, with histological analysis of insulitis. Ultrasound contrast signal was elevated in the pancreas of 10-wk-old NOD mice following ND infusion and vaporization but was absent in both the noninfiltrated kidney of NOD mice and the pancreas of Rag1ko controls. High-contrast elevation also correlated with rapid diabetes onset. Elevated contrast was also observed as early as 4 wk, prior to mouse insulin autoantibody detection. In the pancreata of NOD mice, infiltrated islets and nearby exocrine tissue were selectively labeled with fluorescent NDs. Thus, contrast ultrasound imaging with ND phase-change agents can detect insulitis prior to diabetes onset. This will be important for monitoring disease progression, to guide and assess preventative therapeutic interventions for T1D.

Impact of income and eating speed on new-onset diabetes among men: a retrospective cohort study

ObjectiveTo examine the impact of income and eating speed on new-onset diabetes among men.DesignThis was a retrospective cohort study.SettingWe used the administrative claims and health check-up data for fiscal years 2010–2015 obtained from the Fukuoka branch of the Japan Health Insurance Association.ParticipantsParticipants were 15 474 non-diabetic male employees, aged between 40 and 74 years. They were categorised based on their eating speeds (ie, fast, normal and non-fast).Primary and secondary outcome measuresTo calculate the OR of the development of diabetes, we created generalised linear regression models with diabetes onset as the dependent variable and eating speed and income as covariates and calculated corresponding 95% CI values. The analyses were performed after adjusting the data for age, obesity and comorbidities.ResultsOf the total participants, 620 developed diabetes during the 5-year study period. A univariate analysis using the generalised linear regression model revealed that eating fast (OR: 1.35, 95% CI 1.17 to 1.55) and having a low income wereincome (OR: 1.47, 95% CI 1.24 to 1.74) were significantly associated with the onset of diabetes. After adjusting for age, obesity and comorbidities, both eating fast (OR: 1.17, 95% CI 1.02 to 1.35) and having a low income (OR: 1.24, 95% CI 1.03 to 1.50) were recognised as independent risk factors for diabetes onset.ConclusionsThe study revealed that eating fast and having a low income were independent risk factors, leading to the development of diabetes. While it is difficult to address income differences, it may be possible to address the factors that contribute to income differences to manage diabetes appropriately and at low healthcare costs. However, eating speed can be controlled. Hence, the provision of education and coaching on dietary habits, including eating speed, may be effective in preventing diabetes onset.