Glucose control using fast-acting insulin aspart in a real-world setting: A 1-year, two-centre study in people with type 1 diabetes using continuous glucose monitoring.

AIM: To evaluate the efficacy and safety of switching from traditional mealtime insulins to fast-acting insulin aspart (Fiasp) in a "real-world" clinical practice setting in adult people with type 1 diabetes (PWD1) who were using intermittently scanned or real-time continuous glucose monitoring (isCGM or rtCGM, respectively). MATERIALS AND METHODS: Data from 438 adult PWD1 (60% men, age 44.6 ± 16.2 years, diabetes duration 21.5 ± 14.0 years, isCGM/rtCGM: 391/47, multiple daily injections/continuous subcutaneous insulin infusion: 409/29), who initiated Fiasp from January 2018 to May 2020, were analysed. The primary objective was the evolution of time in range (TIR; 70-180 mg/dL) at 6 and 12 months. Secondary objectives included change in HbA1c, body mass index (BMI), insulin doses, time below range (<70 and <54 mg/dL), and time above range (>180 and >250 mg/dL). RESULTS: TIR improved from 50.3% ± 15.6% to 54.3% ± 15.1% at 6 months (n = 425) and to 55.5% ± 15.2% at 12 months (n = 385) (P < .001), corresponding to 57 min/d at 6 months and 75 min/d at 12 months. Time spent below 54 mg/dL evolved from 3.1% ± 3.3% to 3.1% ± 3.7% and 2.5% ± 3.0% at 6 and 12 months, respectively (P = .011). Also, time spent above 180 mg/dL decreased from 42.3% ± 16.7% at start by 4.2% at 6 months and by 4.6% at 12 months (P < .001). The proportion of people reaching TIR more than 70% increased from 11.0% to 14.8% (P = .002), and those spending less than 4% at time less than 70 mg/dL increased from 36.1% to 42.1% (P = .002). After 12 months, HbA1c, insulin doses, and BMI did not change significantly. CONCLUSIONS: In a Belgian real-world setting of adult PWD1, switching to Fiasp was associated with a 5% increased TIR after 12 months, corresponding to 75 min/d, in combination with less time spent below and above range.

Features of oral glucose tolerance tests in patients after Roux-en-Y gastric bypass with and without hypoglycaemia symptoms in daily life: It's all about speed.

OBJECTIVE: To evaluate the glucose and insulin profiles during an oral glucose tolerance test (OGTT) after Roux-en-Y gastric bypass (RYGB) in symptomatic and asymptomatic patients. RESEARCH DESIGN AND METHODS: This retrospective study consisted of two groups that had undergone RYGB. The symptomatic (S) group (n = 27) had an OGTT at presentation, whereas the asymptomatic (A) group (n = 99) had an OGTT 1 year after RYGB. Each group was subdivided into two groups, namely, those with glycaemia <54 mg/dL (S1/A1) and those with glycaemia >54 mg/dL (S2/A2) during OGTT. Most of the patients underwent OGTT preoperatively. RESULTS: Preoperatively, the glucose and insulin levels, as well as the speed of increase and decrease, were similar in all groups. Postoperatively, the minimum glucose levels during the OGTT did not differ between the symptomatic and asymptomatic groups (55 ± 19 vs. 54 ± 17 mg/dL) or between the S1 and A1 subgroups (39 ± 7 vs. 43 ± 8 mg/dL). The peak glucose values were higher in the symptomatic versus the asymptomatic group (236 ± 52 vs. 189 ± 43 mg/dL; P <0.05) and in the S1 and S2 versus the A1 and A2 subgroups. The speed of glucose increase and decline was significantly higher in the symptomatic group versus the asymptomatic group, with the speed of glucose decline being the highest in the S1 subgroup. CONCLUSION: Assessing hypoglycaemia after a gastric bypass remains challenging. Our study suggests that the main difference in glucose dynamics between symptomatic and asymptomatic patients might be the speed of glucose and insulin increase and decline during OGTT rather than the absolute values obtained.

Basal metabolic rate using indirect calorimetry among individuals living with overweight or obesity: The accuracy of predictive equations for basal metabolic rate.

BACKGROUND & AIMS: Weight reduction programs in people with overweight or obesity can be informed by indirect calorimetry (IC) which is the gold standard to measure basal metabolic rate (BMR). Since IC is labor intensive and expensive, predictive equations are often used as an alternative. In this study the accuracy rate was assessed and bias statistics of predictive equations were compared to IC among subjects with overweight or obesity. Secondly, differences in clinical features between individuals with over-, accurate or underestimation of their BMR were evaluated. METHODS: This cross sectional study included 731 subjects from the outpatient obesity clinic of the Antwerp University Hospital, Belgium. Fourteen equations were evaluated. Overestimation and underestimation was defined as >10 % and <10 % of measured BMR. RESULTS: In the total population, mean age was 43 ± 13 years, mean BMI 35.6 ± 5.8 kg/m2 and 79.5 % were female. The highest accuracy rates were reached by the Henry (73 %), Ravussin (73 %) and Mifflin St. Jeor (73 %) equations. In the total population, the Mifflin St. Jeor and Henry equation were unbiased. The Akern, Livingston and Ravussin equations were biased to underestimation. All other equations were biased to overestimation. Subjects with an underestimation of BMR had significantly higher waist-hip ratio (1.02 ± 0.13 vs 0.91 ± 0.11; P < 0.001), higher visceral adipose tissue (239 ± 96 vs 162 ± 93; P < 0.001), lower fat free mass (kg) (67.6 (45.4-95.9) vs 54.0 (39.6-95.5); P < 0.001) and a higher prevalence of the Metabolic Syndrome (24 (77.4) vs 112 (37.5); P < 0.001). Individuals with an overestimation of BMR had significantly higher subcutaneous adipose tissue (545 ± 149 vs 612 ± 149; P < 0.05), lower fasting plasma insulin (81 (10-2019) vs 67 (27-253); P < 0.001) and lower 2-h plasma glucose (132 (30-430) vs 116 (43-193); P < 0.001) during OGTT. CONCLUSIONS: In this study, the Henry and Mifflin St. Jeor equations have the highest accuracy and lowest bias to estimate the basal metabolic rate in a Caucasian, predominantly female, population living with overweight or obesity. Visceral and subcutaneous adipose tissue and presence of metabolic syndrome were significantly different in individuals with over- or underestimation of BMR.

Malnutrition and its relation with diabetic foot ulcer severity and outcome: a review.

BACKGROUND: Malnutrition has a detrimental effect on wound healing; hence, it might influence the outcome in people with a diabetic foot ulcer (DFU).The aim of this manuscript is to overview studies that describe the prevalence of malnutrition in DFU patients and assess the relation between malnutrition, DFU severity, and outcome. METHODS: A literature review was performed. Malnutrition had to be defined by anthropometry and/or validated screening and assessment tools. RESULTS: Five papers were included: one RCT, three prospective cohort studies and one retrospective observational study. A substantial number of patients were at risk for malnutrition (49%-70%) or were malnourished (15%-62%). In one study, nutritional status was related to DFU severity. Three authors demonstrated a negative influence of malnutrition on outcome. Two studies examined the prevalence of malnutrition after six months, but did not detect a decline in malnutrition rates. CONCLUSIONS: Despite a large heterogeneity, all papers indicated that malnutrition is highly prevalent among DFU patients. Notwithstanding the lack of unequivocal evidence, malnutrition might have a negative influence on DFU outcome. Therefore, clinicians should pay attention to the nutritional status of people with a DFU.Abbreviations: BMI: Body Mass Index; DFU: Diabetic Foot Ulcer; DM: Diabetes Mellitus; GNRI: Geriatric Nutritional Risk Index; HbA1c: Glycated Hemoglobin; IWGDF: International Working Group on the Diabetic Foot; LEA: Lower Extremity Amputation; MNA: Mini Nutritional Assessment; MNA-SF: Mini Nutritional Assessment-Short Form; MUST: Malnutrition Universal Screening Tool; NRS-2002: Nutritional Risk Screening-2002; PAD: Peripheral Arterial Disease; RCT: randomized controlled trial; SGA: Subjective Global Assessment.

Malnutrition according to the 2018 GLIM criteria is highly prevalent in people with a diabetic foot ulcer but does not affect outcome.

OBJECTIVE: To estimate the prevalence of protein-energy malnutrition in people admitted for a diabetic foot ulcer (DFU) and to assess the relationship between malnutrition and DFU severity and outcome. METHODS: This prospective, observational cohort study included individuals consecutively admitted for a DFU between July 2016 and September 2019. The Global Leadership Initiative on Malnutrition (GLIM) criteria determined the prevalence of malnutrition. The SINBAD score reflected DFU severity. Outcome was evaluated at discharge and at 6 months. The independent contribution of nutritional status on DFU severity and outcome was investigated using logistic regression analysis. RESULTS: A total of 110 patients were included. Malnutrition, as defined by the GLIM criteria, was diagnosed in 26 cases; malnutrition was moderate in 9 and severe in 17. DFU severity differed significantly between subjects with malnutrition versus without malnutrition (SINBAD: 3.85 vs. 3.81, p = 0.012). Logistic regression analysis showed that severe malnutrition (p = 0.015) and hemoglobin level (p = 0.003) were independently linked to DFU severity. At 6-month follow-up, 39 DFU were healed, 36 patients had undergone an amputation (32 minor, 4 major) and 8 had died. No differences were noted in outcome at discharge or at 6 months according to nutritional status. CONCLUSIONS: In 24% of patients, malnutrition was diagnosed. Severely malnourished individuals presented with more severe ulcers. However, malnutrition had no impact on the short-term outcome of a DFU.

Cardiometabolic importance of 1-h plasma glucose in obese subjects.

BACKGROUND/OBJECTIVES: To study the importance and clinical usefulness of the 1-h plasma glucose (1hPG) in a Caucasian obese population with regard to the presence of prediabetes, diabetes, and metabolic syndrome (MetS). SUBJECTS/METHODS: We conducted a cross-sectional study of 2439 overweight or obese subjects. All received an oral glucose tolerance test (OGTT) using the American Diabetes Association criteria. ROC-curves were used to compare the sensitivity and (1-specificity) of 1hPG versus FPG and 2hPG to diagnose prediabetes and diabetes. RESULTS: Of 2439 patients (72.1% female) (age 43 ± 13 years, BMI 37.9 (34.6-41.6) kg/m2), 1262 (51.7%) had a 1hPG ≥ 155 mg/dL. The prevalence of prediabetes was 33.8% and of diabetes 9.8%. In these 240 diabetic patients, only 1.6% (four patients) did not show a 1hPG ≥ 155 mg/dL. Subjects with 1hPG ≥ 155 mg/dL were more insulin resistant (p < 0.001), had a higher waist (p < 0.001), visceral adipose tissue (VAT) (p < 0.001), systolic blood pressure (p < 0.001), microalbuminuria (p < 0.001), PAI-1 (p < 0.001), and worse lipid profile (p < 0.001) than subjects with 1hPG < 155 mg/dL. MetS was present in 64.1% of subjects with 1hPG ≥ 155 mg/dL versus 42.5% of subjects with 1hPG < 155 mg/dL (p < 0.001). In the group with 1hPG ≥ 155 mg/dL 32.6% had a normal glucose tolerance (NGT), 48.9% had prediabetes, and 18.5% was diagnosed with T2DM compared to 81.7% NGT, 17.7% prediabetes, and 0.6% T2DM in subjects with 1hPG < 155 mg/dL (p < 0.001). Among NGT subjects, 30.0% had a 1hPG ≥ 155 mg/dL and showed higher HOMA-IR (p = 0.008), VAT (p < 0.001), blood pressure (p < 0.001), and worse lipid profile (p = 0.001). Compared to 1hPG < 155 mg/dL, the sensitivity and specificity of 1hPG ≥ 155 mg/dL of prediabetes were 74.8% and 60.0% and for diabetes 97.1% and 53.2%, respectively. CONCLUSIONS: This study supports the role of 1hPG value as a valuable tool in the detection of obese subjects at high risk for T2DM and MetS.

Identification and functional characterization of a missense mutation in resistin in two patients with severe obesity and insulin resistance.

OBJECTIVE: In this study, we hypothesized that mutations in the resistin encoding gene, RETN, may cause a monogenic form of obesity. DESIGN/METHODS: We screened the coding region of RETN in 81 morbidly obese adults, 263 overweight and obese children/adolescents, and 116 healthy lean subjects. In vitro experiments include qPCR, ELISA, and western blot for WT and mutant resistin transfected into 3T3-L1 adipocytes. RESULTS: Mutation analysis identified five sequence variants in our patient populations: 3'-UTR +87 G/A, 3'-UTR +100 A/G, T73T, IV3-61 C/A, and C78S. In our control population, we only found the 3'-UTR +87 G/A variant. We started functional experiments for the C78S mutation that was found in a 20-year-old obese male (body mass index (BMI)=39.7 kg/m(2)) and his obese mother (BMI=31.9 kg/m(2)). In vitro testing demonstrated that the mutation does not impair mRNA expression. We identified a 100-fold lower extracellular protein concentration for mutant resistin compared with WT levels using a resistin ELISA on cell culture medium (P=4.87×10(-6)). We also detected a decreased intracellular concentration for the mutant protein (tenfold lower relative levels, P=0.007). The plasma resistin levels of the proband and his mother, however, did not differ significantly from lean control individuals. CONCLUSIONS: In conclusion, we identified the first missense mutation in resistin in a morbidly obese proband and his obese mother. Functional testing of the mutant protein suggests that the C78S mutant protein is degraded, possibly resulting in a decreased extracellular concentration, which may predispose to obesity.