Purnell JQ, Marshall N, Francisco M
… +8 more, Leo M, Rooney WD, Baetscher E, Frias A, Valent A, Catalano P, King J, Vesco KK
Diabetes Care
· 2026 Jul · PMID 41746698
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OBJECTIVE: To determine relationships between measurements of total body, visceral, and ectopic (liver, skeletal muscle) fat with insulin sensitivity in pregnancy. RESEARCH DESIGN AND METHODS: Pregnant women of varying p...OBJECTIVE: To determine relationships between measurements of total body, visceral, and ectopic (liver, skeletal muscle) fat with insulin sensitivity in pregnancy. RESEARCH DESIGN AND METHODS: Pregnant women of varying prepregnancy weights were prospectively studied in early (n = 59) and late (n = 47) gestation. At each visit, participants underwent body composition measurements including fat mass (FM), fat-free mass (FFM), abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), ectopic lipid amounts in liver (intrahepatic lipid [IHL]) and calf skeletal muscle (intramyocellular lipid [IMCL] and extramyocellular lipid), and hyperinsulinemia-euglycemic clamp to determine insulin sensitivity (Rd), endogenous glucose production (EGP), hepatic insulin sensitivity index (HISI), and free fatty acid (FFA) levels. RESULTS: In early pregnancy, Rd ([mg/kg FFM/min]/µIU/mL) inversely correlated (P values <0.05) with BMI, FM, SAT, VAT, IHL, IMCL, and FFA. HISI inversely correlated (P values <0.05) with BMI, FM, SAT, VAT, IMCL, and FFA but not with IHL. In late pregnancy, however, neither EGP ([mg/kg FFM/min]/µIU/mL) nor Rd correlated with regional or ectopic fat measures, but HISI remained inversely correlated with BMI, FM, SAT, VAT, and IMCL. Early-pregnancy IHL levels did not predict late-pregnancy insulin sensitivity. Pregnant women with prepregnancy obesity were more insulin resistant but gained less gestational weight, VAT, and SAT, and experienced less decline in insulin sensitivity, than normal prepregnancy weight women. CONCLUSIONS: Insulin resistance in early pregnancy is strongly associated with total, regional, and ectopic adiposity. However, in late pregnancy, factors other than regional and ectopic adiposity predominately influence insulin sensitivity. Prepregnancy weight categories proportionately alter gestational weight gain, adiposity distribution, and glucometabolic responses.
OBJECTIVE: To characterize the distribution of time in tight and broader glycemic ranges in adults without diabetes and to examine cross-sectional and longitudinal associations with metabolic health. RESEARCH DESIGN AND...OBJECTIVE: To characterize the distribution of time in tight and broader glycemic ranges in adults without diabetes and to examine cross-sectional and longitudinal associations with metabolic health. RESEARCH DESIGN AND METHODS: We analyzed continuous glucose monitoring data from 8,687 adults (40-70 years, 54% women) in the Human Phenotype Project, each contributing 1,149 ± 279 glucose readings from FreeStyle Libre Pro sensors. Age- and sex-adjusted correlations linked time-in-range metrics with 45 clinical phenotypes encompassing adiposity, vascular, and liver markers, sleep indices, and nutrition. Cox models tested associations of time above glycemic thresholds with incident metabolic disease over 2.6 ± 1.3 years. RESULTS: Participants spent a median 93.0% (interquartile range [IQR] 91.8-98.2) of continuous glucose monitor time within 70-140 mg/dL and 95.2% (IQR 95.1-99.8) within 70-180 mg/dL. Time below 140 mg/dL and 180 mg/dL was 97.7% (IQR 97.6-97.8) and 99.9% (IQR 99.9-99.9), respectively. Less time at <140 mg/dL correlated with higher waist circumference, visceral fat, triglycerides, blood pressure, serum ALT, and liver attenuation, and with lower HDL cholesterol and mean nocturnal oxygen saturation. Associations weakened using the <180 mg/dL threshold. Less time at <180 mg/dL and <140 mg/dL was associated with higher risk of incident metabolic disease (hazard ratio 1.21 [95% CI 1.15-1.26] and 1.34 [95% CI 1.26-1.42], respectively). CONCLUSIONS: We provide population references for time spent in different glycemic ranges by adults without diabetes. Although our study is observational and not designed to establish causality, our findings suggest that even within normoglycemic ranges, less time at <140 mg/dL is associated with unfavorable health parameters and higher incident metabolic disease risk.
OBJECTIVE: Diabetic foot ulcer (DFU) is the leading cause of nontraumatic lower-limb amputation (LLA). The impact of sodium-glucose cotransporter 2 inhibitor (SGLT2i) use on LLA is still debated in studies in which the p...OBJECTIVE: Diabetic foot ulcer (DFU) is the leading cause of nontraumatic lower-limb amputation (LLA). The impact of sodium-glucose cotransporter 2 inhibitor (SGLT2i) use on LLA is still debated in studies in which the proportion of patients with DFU is unknown. The aim of our study was to determine, specifically in patients with DFU, if the use of an SGLT2i could influence amputation and wound healing. RESEARCH DESIGN AND METHODS: This retrospective, monocentric study was conducted in a French specialized diabetic foot center. All patients treated for a new DFU between January 2022 and May 2024 and who had 1 year of follow-up were included. The primary end point was 1-year amputation rate. RESULTS: Of the 452 patients included in this study, 94 were treated with an SGLT2i and 358 were not. The mean ± SD age of the study population was 70.2 ± 11.6 years and 77% of patients were men. In the adjusted statistical model, there was no significant association between the 1-year amputation rate and SGLT2i use (P = 0.688). The 6-month healing rate was not significantly different between patients treated or not treated with SGLT2is (54.4% vs. 44.5%; P = 0.091). Healing time was significantly less in patients treated with SGLT2is, with a mean ± SD difference of 44 days (136.5 ± 97.8 vs. 181.2 ± 159.8; P = 0.04). The 1-year mortality rate was significantly lower in the SGLT2i group (1.1% vs. 9.2%; P = 0.009). CONCLUSIONS: The use of SGLT2is does not negatively impact the 1-year amputation rate or healing rate of DFU. One-year mortality was lower in patients treated with an SGLT2i.
OBJECTIVE: It has been postulated that pregnancies may contribute to the lifetime risk of type 2 diabetes mellitus (T2DM) in women, although direct evidence is lacking. In this context, we hypothesized that pregnancy may...OBJECTIVE: It has been postulated that pregnancies may contribute to the lifetime risk of type 2 diabetes mellitus (T2DM) in women, although direct evidence is lacking. In this context, we hypothesized that pregnancy may impact the long-term natural history of the pathophysiologic determinants of T2DM: insulin sensitivity and β-cell function. We sought to evaluate 10-year trajectories of these features in parous women with and without an additional pregnancy. RESEARCH DESIGN AND METHODS: Metabolic characterization was done in 303 women at 1 year postpartum and on three or more occasions over the decade thereafter. Each assessment included an oral glucose tolerance test, enabling serial evaluation of insulin sensitivity/resistance (Matsuda index; HOMA-insulin resistance [IR]), β-cell function (Insulin Secretion-Sensitivity Index-2; insulinogenic index/HOMA-IR), and glycemia. Linear mixed-effect models adjusted for diabetes risk factors were constructed to evaluate the natural time trend of these measures over 10 years in those with (n = 78) and without (n = 225) an additional pregnancy. RESULTS: At baseline, women who subsequently had an additional pregnancy were younger (P < 0.001) and more likely to be primiparous (P < 0.001) than their peers. Notably, they had higher covariate-adjusted insulin sensitivity (Matsuda index) at baseline (estimated adjusted average difference 1.64; 95% CI 0.22-2.86) and at 1.5 years' follow-up (1.28; -0.15 to 2.50), but this difference disappeared by 3.5 years and 5.5 years. The 10-year trajectory of the Matsuda index differed between the groups (time-group interaction P = 0.02), with no differences in trajectories of β-cell function and glycemia. CONCLUSIONS: Pregnancy is associated with worsening of the long-term trajectory of insulin sensitivity, revealing both a pathophysiologic basis for enhanced diabetes risk and a target for risk modification.
van der Meer R, Pazmino S, Steenackers N
… +19 more, van Laar A, Sluis M, Tolenaars L, Rosen J, Hurtado Del Pozo C, le Roux CW, Al Kandari J, Irshad M, Lannoo M, Deleus E, Dillemans B, Van Nieuwenhove Y, van Bon A, Hazebroek E, Al Ozairi E, Hoogma R, Mathieu C, Liem R, Van der Schueren B
Diabetes Care
· 2026 Apr · PMID 41706050
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OBJECTIVE: To assess the effect of metabolic bariatric surgery (MBS) in people living with type 1 diabetes (T1D) and obesity. RESEARCH DESIGN AND METHODS: From retrospective multicenter data, total weight loss, daily ins...OBJECTIVE: To assess the effect of metabolic bariatric surgery (MBS) in people living with type 1 diabetes (T1D) and obesity. RESEARCH DESIGN AND METHODS: From retrospective multicenter data, total weight loss, daily insulin requirement, HbA1c, and cardiometabolic parameters were assessed before and after surgery. Longitudinal models were used to identify response determinants. RESULTS: This study included 162 people living with T1D and obesity. One year after surgery, mean total weight loss percentage was 29.7% (interquartile range [IQR] = 29.4, 30.3). Insulin requirements dropped from 0.75 (IQR = 0.58, 1.00) units/kg/day to 0.32 (IQR = 0.23, 0.43) units/kg/day (P < 0.001), and HbA1c dropped from 64.0 (IQR = 57.0, 74.0) mmol/mol to 60.0 (IQR = 53.4, 68.0) mmol/mol (P < 0.001). LDL, HDL, total cholesterol, and triglyceride levels significantly improved after surgery (P < 0.001). Greater total weight loss was associated with reduced insulin requirements, and higher baseline HbA1c was associated with poorer postsurgery glycemic control. CONCLUSIONS: MBS was associated with substantial metabolic improvement in people with T1D and obesity, in particular in those with high HbA1c and insulin need at baseline.