Diabetes Mellitus, Energy Metabolism, and COVID-19.

Obesity, diabetes mellitus (mostly type 2), and COVID-19 show mutual interactions because they are not only risk factors for both acute and chronic COVID-19 manifestations, but also because COVID-19 alters energy metabolism. Such metabolic alterations can lead to dysglycemia and long-lasting effects. Thus, the COVID-19 pandemic has the potential for a further rise of the diabetes pandemic. This review outlines how preexisting metabolic alterations spanning from excess visceral adipose tissue to hyperglycemia and overt diabetes may exacerbate COVID-19 severity. We also summarize the different effects of SARS-CoV-2 infection on the key organs and tissues orchestrating energy metabolism, including adipose tissue, liver, skeletal muscle, and pancreas. Last, we provide an integrative view of the metabolic derangements that occur during COVID-19. Altogether, this review allows for better understanding of the metabolic derangements occurring when a fire starts from a small flame, and thereby help reducing the impact of the COVID-19 pandemic.

Telemedicine and urban diabetes during COVID-19 pandemic in Milano, Italy during lock-down: epidemiological and sociodemographic picture.

BACKGROUND: Since 2010, more than half of World population lives in Urban Environments. Urban Diabetes has arisen as a novel nosological entity in Medicine. Urbanization leads to the accrual of a number of factors increasing the vulnerability to diabetes mellitus and related diseases. Herein we report clinical-epidemiological data of the Milano Metropolitan Area in the contest of the Cities Changing Diabetes Program. Since the epidemiological picture was taken in January 2020, on the edge of COVID-19 outbreak in the Milano Metropolitan Area, a perspective addressing potential interactions between diabetes and obesity prevalence and COVID-19 outbreak, morbidity and mortality will be presented. To counteract lock-down isolation and, in general, social distancing a pilot study was conducted to assess the feasibility and efficacy of tele-monitoring via Flash Glucose control in a cohort of diabetic patients in ASST North Milano. METHODS: Data presented derive from 1. ISTAT (National Institute of Statistics of Italy), 2. Milano ATS web site (Health Agency of Metropolitan Milano Area), which entails five ASST (Health Agencies in the Territories). A pilot study was conducted in 65 screened diabetic patients (only 40 were enrolled in the study of those 36 were affected by type 2 diabetes and 4 were affected by type 1 diabetes) of ASST North Milano utilizing Flash Glucose Monitoring for 3 months (mean age 65 years, HbA1c 7,9%. Patients were subdivided in 3 groups using glycemic Variability Coefficient (VC): a. High risk, VC > 36, n. 8 patients; Intermediate risk 20 < VC < 36, n. 26 patients; Low risk VC < 20, n. 4 patients. The control group was constituted by 26 diabetic patients non utilizing Flash Glucose monitoring. RESULTS: In a total population of 3.227.264 (23% is over 65 y) there is an overall prevalence of 5.65% with a significant difference between Downtown ASST (5.31%) and peripheral ASST (ASST North Milano, 6.8%). Obesity and overweight account for a prevalence of 7.8% and 27.7%, respectively, in Milano Metropolitan Area. We found a linear relationship (R = 0.36) between prevalence of diabetes and aging index. Similarly, correlations between diabetes prevalence and both older people depending index and structural dependence index (R = 0.75 and R = 0.93, respectively), were found. A positive correlation (R = 0.46) with percent of unoccupied people and diabetes prevalence was also found. A reverse relationship between diabetes prevalence and University level instruction rate was finally identified (R = - 0.82). Our preliminary study demonstrated a reduction of Glycated Hemoglobin (p = 0.047) at 3 months follow-up during the lock-down period, indicating Flash Glucose Monitoring and remote control as a potential methodology for diabetes management during COVID-19 lock-down. HYPOTHESIS AND DISCUSSION: The increase in diabetes and obesity prevalence in Milano Metropolitan Area, which took place over 30 years, is related to several environmental factors. We hypothesize that some of those factors may have also determined the high incidence and virulence of COVID-19 in the Milano area. Health Agencies of Milano Metropolitan Area are presently taking care of diabetic patients facing the new challenge of maintaining sustainable diabetes care costs in light of an increase in urban population and of the new life-style. The COVID-19 pandemic will modify the management of diabetic and obese patients permanently, via the implementation of approaches that entail telemedicine technology. The pilot study conducted during the lock-down period indicates an improvement of glucose control utilizing a remote glucose control system in the Milano Metropolitan Area, suggesting a wider utilization of similar methodologies during the present "second wave" lock-down.

Performance of the Steno type 1 risk engine for cardiovascular disease prediction in Italian patients with type 1 diabetes.

BACKGROUND AND AIMS: Premature cardiovascular disease cause excess mortality in type 1 diabetes (T1D). The Steno T1D Risk Engine was developed and validated in northern European countries but its validity in other populations is unknown. We evaluated the performance of the Steno T1D Risk Engine in Italian patients with T1D. MATERIALS AND METHODS: We included patients with T1D with a baseline visit between July 2013 and April 2014, who were free of cardiovascular disease and had complete information to estimate risk. The estimated cardiovascular risk score was compared with the 5-year rate of cardiovascular events by means of logistic regression. RESULTS: Among 223 patients (mean age 43 ± 13 years, 34.5% male, mean duration of diabetes 22 ± 12 years) the mean estimated cardiovascular risk at 5 years was 5.9% (95% C.I. 5.2-6.5%). At baseline, high estimated risk discriminated the presence of asymptomatic atherosclerosis better than microangiopathy, and was not associated with markers of inflammation or endothelial activation. After a mean follow-up of 4.7 ± 0.5 years, only 3 cardiovascular events were observed and nonetheless the risk score was significantly associated with their incidence (OR 1.22; 95% C.I. 1.08-1.39, p = 0.001). However, the observed event rate was significantly lower than the estimated one (3 vs 13; 95% C.I. 12-14; p < 0.001). CONCLUSION: The Steno T1D Risk Score identified subjects with subclinical atherosclerosis and high cardiovascular risk in an Italian T1D population. However, the absolute risk was significantly overestimated. Further studies in larger population are needed to confirm these results.

Insulin Management for Type 1 Diabetic Patients During Social Alcohol Consumption: The SPRITZ Study.

BACKGROUND: There is no data available on the best insulin treatment to counteract the effects of glucose excursions due to a moderate alcohol intake associated with portions of slight fat and protein-containing food, as often the case during social happenings or "happy hours". INTRODUCTION: This study analyzes the glycemic control and quality of life in 8 adult type 1 diabetic (T1D) patients on insulin-pump therapy which were invited to consume a traditional Italian aperitif ("Spritz" and chips). METHODS: Patients consumed Spritz aperitif twice: using their habitual bolus, based on carbohydrates (CHO) counting (V1), or with a personalized, advanced bolus (V2) calculated from insulin/Kcal derived from Fats and Proteins (FPU). Post-prandial glucose was continuously monitored; glucose incremental areas (iAUC), glucose peak and time to peak, and estimated change from V1 to V2 from repeated- measures models were computed. Each patient fulfilled validated questionnaires on quality of life, knowledge about diabetes and CHO counting. RESULTS: After the educational program, a reduced iAUC (0-80 min: -306, p=ns; 40-80 min: -400, p=0.07) due to greater (p=0.03) and prolonged double-wave insulin boluses was observed. Blood glucose peak and time to peak were also reduced. Moreover, improvements in the psycho-affective dimension, as well as in the alimentary knowledge were detected. CONCLUSION: Therefore, a personalized educational program on CHO + FPU counting together with insulin bolus management can improve glycemic control during social consumption of alcohol, with positive reflections on the psycho-affective dimension. Further studies are mandatory to confirm such preliminary results.

Efficacy, safety and acceptability of the new pen needle 34G × 3.5 mm: a crossover randomized non-inferiority trial; AGO 02 study.

OBJECTIVE: Insulin injection aspects, such as fear of injection and pain, directly affect glycemic control, patient adherence and quality of life. Use of thinner and shorter needles could increase acceptance of injections. The aim of the study is to evaluate the non-inferiority of the new 34G × 3.5 mm needle compared to a 32G × 4 mm in patients with diabetes treated with insulin. METHODS: This is an open, randomized, two-period crossover, non-inferiority trial. Every treatment period lasted 3 weeks. Patients with type 1 or type 2 diabetes, treated with multiple daily insulin injections, were randomly assigned to receive a 34G × 3.5 mm or a 32G × 4 mm pen needle. The primary endpoint was the non-inferiority of the 34G × 3.5 mm in comparison with the 32G × 4 mm pen needle in terms of percentage absolute change of blood fructosamine (% |ΔFru|), using a non-inferiority margin of 20%. RESULTS: Overall 77 patients were randomized and 73 completed the study. Patients characteristics were: 52% male, 80.5% affected by type 1 diabetes, mean age 52 years (±14.6), mean BMI 24.5 kg/m2 (±5.6), HbA1c 8% (±1.1) and baseline fructosamine level 350 µmol/l (±84). Mean fructosamine levels increased by 0.56 µmol/l with the 34G needle, while a reduction of 7.29 µmol/l was documented with the 32G needle. The difference between the two groups (7.84 µmol/l) was not statistically significant (p = .27). The % |ΔFru| between the two groups was 7.55% (95% CI 5.67-9.44), meeting the non-inferiority criterion. Glycemic variability, expressed as standard deviation of fasting blood glucose and post-prandial glucose, was not different between the two treatment groups (p = .63 and p = .77, respectively). CONCLUSIONS: The 34G × 3.5 mm needle was non-inferior to the 32G × 4 mm needle regarding fructosamine levels and glycemic variability supporting the suitability of the 34G × 3.5 mm needle for insulin injection in patients with diabetes. CLINICAL TRIAL REGISTRATION: NCT02690467.

Metabolic syndrome and autoimmune diabetes: action LADA 3.

OBJECTIVE: The purpose of this study was to estimate whether prevalence of metabolic syndrome in adult European diabetic patients is associated with type of diabetes. RESEARCH DESIGN AND METHODS: A consecutive series of patients attending hospital-based diabetes clinics were assessed for the frequency of metabolic syndrome and compared with population-based control subjects as part of the Action LADA study. In total, 2,011 subjects (aged 30-70 years) were studied, including 1,247 patients with recent-onset type 2 diabetes without glutamic acid decarboxylase autoantibodies (GADAs), 117 non-insulin-requiring patients with GADAs who had not received insulin therapy for at least 6 months after diagnosis (designated latent autoimmune diabetes of adults [LADA]), 288 type 1 diabetic patients, and 359 normal subjects. RESULTS: Frequency of metabolic syndrome was significantly different in patients with type 1 diabetes (31.9%) and LADA (41.9%) (P = 0.015) and in both conditions was less frequent than in type 2 diabetic patients (88.8%) (P < 0.0001 for each). Eliminating glucose as a variable, the prevalence of metabolic syndrome was similar in patients with autoimmune diabetes (type 1 diabetes and/or LADA) (17.3%) and control subjects (23.7%) but remained more common in type 2 diabetic patients (47.8%) (P = 0.001 for all groups). In both type 1 diabetic patients and those with LADA, individual components of metabolic syndrome were similar but less common than in type 2 diabetic patients (P < 0.0001 for each). CONCLUSIONS: The prevalence of metabolic syndrome is significantly higher in type 2 diabetic patients than in patients with LADA or adults with type 1 diabetes. Excluding glucose as a variable, metabolic syndrome is not more prevalent in patients with autoimmune diabetes than in control subjects. Metabolic syndrome is not a characteristic of autoimmune diabetes.

Menarche in type 1 diabetes is still delayed despite good metabolic control.

OBJECTIVE: To analyze the age at menarche of girls with type 1 diabetes (T1D) who were diagnosed with the disease before puberty and compare it with that of an age-matched group of normal girls. Previous studies on the appearance of menarche showed that the mean age of onset of menarche is delayed in girls affected by T1D compared with normal girls. DESIGN: Case-control study. SETTING: Patients and controls in an academic research environment. PATIENT(S): We studied, retrospectively, the charts of 162 consecutive girls with T1D born in a geographically defined region between 1984 and 1994 with a mean disease duration of 3-5 years, all of whom were on intensive insulin therapy since diagnosis of T1D. The control group consisted of 214 normal girls born between 1984 and 1994, who agreed to fill in an anonymous questionnaire regarding age at menarche and other clinical information. INTERVENTION(S): There was no intervention per se in the study. Age at menarche appears as a dependent variable of body mass index (BMI), HbA1c, and so on. MAIN OUTCOME MEASURE(S): BMI, HbA1c, and duration of T1D at menarche were considered among the potential factors affecting the age of menarche. RESULT(S): Age at menarche in girls with T1D was significantly delayed compared with control girls (12.6 +/- 1.5 years vs. 12.25 +/- 1.4 years, respectively). HbA1c levels and BMI did not influence the age at menarche. CONCLUSION(S): Despite intensive insulin therapy and good metabolic control since diagnosis of T1D, the age at menarche is still delayed in girls who develop T1D before puberty.