BMJ Open Diabetes Research & Care最新文献

Introduction: To compare carotid intima-media thickness (cIMT) and liver fat content in subjects who maintained good glycemic control for 6 years on initial triple therapy with metformin/exenatide/pioglitazone versus sequential add-on therapy with metformin followed with glipizide and basal insulin in subjects with new-onset diabetes.

Research design and methods: Liver fat content and cIMT were compared among patients with T2DM who received initial triple therapy with metformin/pioglitazone/exenatide (n=29) versus metformin, followed by stepwise addition of glipizide and then insulin glargine (n=26) and who maintained HbA1c<6.5% for 6 years in Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes.

Results: After 6 years in subjects receiving initial triple therapy with metformin/pioglitazone/exenatide and subjects receiving sequential addition of metformin followed by glipizide and insulin glargine had a mean HbA1c of 5.7% vs 6.0%, respectively, p=NS. Nonetheless, subjects receiving sequential add-on therapy experienced a greater increase in cIMT and manifested greater liver fat content and fibrosis than subjects receiving initial triple therapy.

Conclusions: Including pioglitazone plus exenatide in the glucose-lowering regimen slows the progression of cIMT and was associated with lower hepatic fat content and fibrosis compared with subjects receiving sequential add-on therapy without pioglitazone and exenatide despite comparable optimal glycemic control.

Trial registration number: NCT01107717.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dual glucose insulinotropic polypeptide (GIP)/GLP-1 RA are widely prescribed, but their effectiveness in different subtypes of maturity-onset diabetes of the young (MODY) is unknown.

Research design and methods: We present a descriptive case series of individuals from two MODY cohorts who used GLP-1 RA or dual GIP/GLP-1 RA. Paired t tests were used to compare HbA1c, body mass index (BMI), and sulfonylurea (SU) dose before and after GLP-1 RA or dual GIP/GLP-1 RA therapy.

Results: 10 individuals (4 hepatocyte nuclear factor-1α (HNF1A)-MODY, 4 hepatocyte nuclear factor-4α (HNF4A)-MODY, 1 ATP-binding cassette transporter subfamily C member 8 (ABCC8)-MODY, 1 hepatocyte nuclear factor-1β (HNF1B)-MODY) were identified who used GLP-1 RA or dual GIP/GLP-1 RA. In patients with HNF1A-MODY and HNF4A-MODY, GLP-1 RA reduced HbA1c by 1.3% (p=0.010), BMI by 2.90 kg/m² (p=0.008), and total daily dose of SU by 66.6% (p=0.005). Dual GIP/GLP-1 RA treatment led to a non-statistically significant decrease in HbA1c of 1.8% (p=0.104), a statistically significant reduction in BMI of 8.73 kg/m² (p=0.010), and all patients discontinued SU (n=2) and one discontinued insulin. In patients with ABCC8-MODY and HNF1B-MODY, GLP-1 RA reduced HbA1c by 1.2% and 1.8%, BMI by 1.1 kg/m² and 1.2 kg/m², and the patients no longer required treatment with SU or insulin, respectively.

Conclusions: GLP-1 RA and dual GIP/GLP-1 RA lowered HbA1c, BMI, and SU dose in patients with MODY.

Introduction: About one-third of adults in the USA have some grade of hepatic steatosis. Coronary artery calcium (CAC) scans contain more information than currently reported. We previously reported new artificial intelligence (AI) algorithms applied to CAC scans for opportunistic measurement of bone mineral density, cardiac chamber volumes, left ventricular mass, and other imaging biomarkers collectively referred to as AI-cardiovascular disease (CVD). In this study, we investigate a new AI-CVD algorithm for opportunistic measurement of liver steatosis.

Methods: We applied AI-CVD to CAC scans from 5702 asymptomatic individuals (52% female, age 62±10 years) in the Multi-Ethnic Study of Atherosclerosis. Liver attenuation index (LAI) was measured using the percentage of voxels below 40 Hounsfield units. We used Cox proportional hazards regression to examine the association of LAI with incident CVD and mortality over 15 years, adjusted for CVD risk factors and the Agatston CAC score.

Results: A total of 751 CVD and 1343 deaths accrued over 15 years. Mean±SD LAI in females and males was 38±15% and 43±13%, respectively. Participants in the highest versus lowest quartile of LAI had greater incidence of CVD over 15 years: 19% (95% CI 17% to 22%) vs 12% (10% to 14%), respectively, p<0.0001. Individuals in the highest quartile of LAI (Q4) had a higher risk of CVD (HR 1.43, 95% CI 1.08 to 1.89), stroke (HR 1.77, 95% CI 1.09 to 2.88), and all-cause mortality (HR 1.36, 95% CI 1.10 to 1.67) compared with those in the lowest quartile (Q1), independent of CVD risk factors.

Conclusion: AI-enabled liver steatosis measurement in CAC scans provides opportunistic and actionable information for early detection of individuals at elevated risk of CVD events and mortality, without additional radiation.

Introduction: Ringer's lactate (RL), a balanced crystalloid by regenerating bicarbonate ion, may lead to early diabetic ketoacidosis (DKA) resolution and reduced hyperchloremia as compared with 0.9% saline (NS).

Research design and methods: This was a double-blind randomized controlled trial conducted in the pediatric emergency and intensive care units of a teaching hospital. Children with type 1 diabetes mellitus (T1DM) aged 9 months to 12 years who presented in DKA were included. Participants were randomized to receive either NS or RL as initial fluid (used for both resuscitation and replacement). The primary outcome was time to resolution of DKA. Secondary outcomes included change in serum chloride and bicarbonate from baseline, total fluid received and incidence of acute kidney injury.

Results: The study was conducted between December 2020 and December 2021, and 67 children were recruited (34 in the NS group and 33 in the RL group). The mean time to DKA resolution was shorter in the RL group compared with the NS group (12.9±7.9 vs 16.8±9 hours). The mean difference and HR for time to DKA resolution in the RL group compared with the NS group were 3.85 hours (95% CI 0.3 to 8) and 1.39 hours (95% CI 1.25 to 1.56), respectively. The rise in chloride from baseline was higher in the NS group as compared with the RL group at 4 and 8 hours (8.7±5.6 vs 3.9±5.1 mmol/L) and (10.8±7.7 vs 4.4±8.3 mmol/L), respectively. On the contrary, the rise in bicarbonate from baseline to 12 hours was significantly higher in the RL group as compared with the NS group (14.7±1.6 vs 12.9±3.1).

Conclusions: The time to resolution of DKA was shorter in RL group as compared with the NS group. Regeneration of bicarbonate from lactate ion in the RL forms a strong physiological basis for this outcome as compared with hyperchloremia induced by NS. This makes RL a favorable option in children with DKA.

Introduction: Recent post hoc analyses indicate that patients with normal or low body mass index (BMI) benefit from sodium-glucose cotransporter-2 (SGLT2) inhibitor use. We aimed to evaluate the effects of SGLT2 inhibitors on renal and patient outcomes in patients with diabetes and normal or low BMI.

Research design and methods: This single-center retrospective cohort study included 5,842 adult patients with type 2 diabetes and BMI<23 kg/m² from 2016 to 2020. Patients were divided into control and SGLT2 inhibitor groups and matched using propensity scores. The primary outcome was the annual change in the estimated glomerular filtration rate (eGFR). Secondary outcomes included change in BMI, a composite renal outcome (eGFR decline of ≥40% from baseline or end-stage kidney disease), all-cause mortality, and cardiovascular disease (CVD).

Results: Overall, 648 patients were selected for propensity score matching, of whom 216 (33.3%) were receiving SGLT2 inhibitors. The mean age and eGFR were 61.6 years and 84.7 mL/min/1.73 m², respectively. The median urine albumin-to-creatinine ratio was 11.6 mg/gCr. The control group showed relatively unchanged eGFR over time, whereas the SGLT2 inhibitor group showed an increase in eGFR over time (0.0 vs +0.3 mL/min/1.73 m²/year, p=0.0398). SGLT2 inhibitor use was associated with a lower risk of mortality (HR 0.171, 95% CI 0.041 to 0.718, p=0.0159) and composite renal outcome (HR 0.223, 95% CI 0.052 to 0.952; p=0.0426), but not with the risk of CVD.

Conclusions: SGLT2 inhibitor use may reduce the risk of eGFR decline and all-cause mortality even in low-risk patients with diabetes and normal or low BMI.

Introduction: Several factors influence individuals' confidence to perform diabetes-related self-care activities, including perceived patient-provider communication, diabetes duration and age at diagnosis. It has been well-documented that patient-provider communication is essential when managing chronic diseases such as diabetes; however, the impact of this communication with diabetes duration and age at diabetes diagnosis on confidence in performing self-care behaviors is obscure.

Research design and methods: We utilized data from the 2021 Household Component of the Medical Expenditure Survey among participants 18 years or older who had completed the Diabetes Care Survey. Ordinal logistic regression models were utilized to assess the association between confidence in performing diabetes self-care (outcome) and perceived communication with healthcare providers (exposure). Age at diabetes diagnosis and diabetes duration were secondary exposures of interest.

Results: 1231 participants were included in the analyses. In primary analyses, we observed that greater perceived healthcare provider communication resulted in greater confidence in diabetes self-care (OR (95% CI) 1.14 (1.08, 1.21)). Results also showed that patients who were diagnosed at older ages have less confidence in managing their diabetes than patients diagnosed at younger ages (OR (95% CI) 0.93 (0.88, 0.99)); correspondingly, longer diabetes duration was associated with greater confidence in diabetes self-care (OR (95% CI) 1.09 (1.01, 1.17)).

Conclusions: Confidence in self-care is greatly influenced by perceptions of patient-provider communication, age at diagnosis and diabetes duration. Specifically, having healthcare providers clearly explain things to patients is vital to increasing diabetes self-care. Because self-care is important when managing chronic diseases such as diabetes, future studies should tailor interventions for optimal outcomes.

Introduction: Roux-en-Y gastric bypass (RYGB) increases the risk of postprandial hypoglycemia, whereas pregnancy decreases insulin sensitivity, which could be expected to counteract hypoglycemia. We examined if RYGB performed prior to pregnancy altered the postprandial glucose metabolism and enteropancreatic hormone responses to a mixed meal test (MMT).

Research design and methods: Twenty-three women with RYGB and 23 women matched on prepregnancy body mass index and parity underwent a 4-hour MMT in the first and third trimester of pregnancy with measurement of circulating levels of glucose, insulin, C-peptide, glucose-dependent insulin peptide (GIP), glucagon-like peptide 1 (GLP-1), glucagon, free fatty acids, and lactate. Biochemical hypoglycemia was defined as plasma glucose <3.5 mmol/L.

Results: Women with RYGB had earlier and higher peak glucose, lower nadir glucose levels, and a higher frequency of biochemical hypoglycemia compared with women without RYGB in both the first and third trimester. The lower glucose levels were preceded by markedly elevated total GLP-1 and insulin levels in women with RYGB, whereas total GIP levels were unaltered. The glucagon levels were lower in women with RYGB. In the first trimester MMT, peak and area under the curve of total plasma GLP-1 and serum insulin levels were negatively associated with nadir plasma glucose, while the early postmeal response of plasma glucagon was positively associated with nadir plasma glucose in the third trimester.

Conclusions: These results provide novel insights into the combined effects of RYGB and pregnancy on postmeal glucose metabolism and enteropancreatic hormone responses during pregnancy, and how these changes associate with an increased risk of postprandial hypoglycemia.

Trial registration number: NCT03713060.

Objective: There is a need for comparable worldwide data on the impact of diabetes on mortality. This study assessed diabetes and all-cause mortality among middle-aged and older adults in five countries.

Research design and methods: We analyzed adults aged 51 years or older followed between 2010 and 2020 from population-based cohorts from China, England, Mexico, rural South Africa, and the USA. The cohorts are part of an international network of longitudinal aging studies with similar sampling designs, eligibility, and assessment methods. Diabetes was defined by self-report or an elevated diabetes blood-based biomarker meeting the clinical criteria for diabetes. All-cause mortality was assessed through linkages or informant interviews. We used Poisson regression models to estimate mortality rate ratios and mortality rate differences, comparing people with diabetes to those without diabetes. Models were adjusted for age, gender, education, smoking status, body mass index, economic status, and, in South Africa, HIV status.

Results: We included 29 397 individuals, of whom 4916 (16.7%) died during the study period. The median follow-up time ranged from 4.6 years in South Africa to 8.3 years in China. The adjusted all-cause mortality rate ratios for people with diabetes versus those without diabetes ranged from 1.53 (95% CI: 1.39 to 1.68) in the USA to 2.02 (95% CI: 1.34 to 3.06) in Mexico. The adjusted mortality rate differences (per 1000 person-years) for people with diabetes vers those without diabetes ranged from 11.9 (95% CI: 4.8 to 18.9) in England to 24.6 (95% CI: 12.2 to 37.0) in South Africa.

Conclusions: Diabetes was associated with increased all-cause mortality in population-based cohorts in China, England, Mexico, rural South Africa, and the USA. Limitations included differences in diabetes biomarkers and selection criteria across cohorts. The results highlight the urgent need to implement clinical and public health interventions worldwide to reduce excess diabetes mortality.

Introduction: In type 2 diabetes (T2D), beta cell failure is often associated with islet inflammation driven by the innate immune response, with macrophages playing a significant role. However, the composition and phenotype of lymphoid immune cells in the islets of individuals with T2D have not been extensively studied. This study aims to characterize and compare the presence, phenotype, and frequency of islet-associated lymphocytes-specifically T, B, and natural killer (NK) cells-in patients with T2D and non-diabetic organ donors.

Research design and methods: Multicolor flow cytometry was employed to detect NK, B, and T cells in dissociated pancreatic islets from 13 T2D and 44 non-diabetic donors. The frequencies and phenotypes of T cell subsets were determined using markers for memory differentiation status and tissue-resident T cells. The frequencies of alpha and beta cells were assessed by flow cytometry, and the insulin secretion level was measured by ELISA.

Results: In both T2D and non-diabetic islets, CD3(+) T cells were the predominant lymphocytes, mainly central and effector memory phenotypes, with a bias toward CD8(+) T cells expressing canonical residency markers (CD69 and CD103). The frequencies of CD19(+) B cells and CD3(-) CD16(+) CD56(+) NK cells were low in both groups. The proportions of these immune and beta cells were similar between T2D and non-diabetic donors. However, T2D donors had a higher proportion of glucagon-producing alpha cells and significantly reduced glucose-stimulated insulin secretion compared with non-diabetic individuals.

Conclusions: In T2D islets, resident CD8(+) T cells with a central memory phenotype dominate the lymphoid immune cell population, similar to non-diabetic donors. These findings provide the first insights into the memory T cell composition in human pancreatic islets in T2D, suggesting that the diabetic condition does not significantly alter the lymphoid landscape of pancreatic islets.

Introduction: Women with type 2 diabetes are at risk of commencing pregnancy while using medications that are either not recommended for pregnancy or with known teratogenicity, which may contribute to adverse pregnancy outcomes. In this study, we aimed to characterize pregnancy-related risk factors and medication exposures among women with type 2 diabetes.

Research design and methods: Individual health characteristics, sociodemographic information, and prescription data were extracted from the primary care records of women aged 18-45 years with type 2 diabetes in participating general practices in the UK. Prescribed medications were categorized according to suitability for pregnancy: recommended, not recommended, or not recommended but used if clinically indicated. Logistic regression was used to estimate associations between individual characteristics and medications not recommended for pregnancy.

Results: Data on 725 women were extracted. Prescribed medications suggested the presence of numerous comorbidities, with diabetes medications (65%, n=471) and statins (20%, n=145) most frequently prescribed. 37% (n=268) of women took ≥3 medications, and a third (n=269) took medications not recommended for pregnancy. Among those not prescribed contraception (89%, n=646), no one met all clinically recommended pre-pregnancy criteria. In multivariable logistic regression analysis, polypharmacy (OR 3.49 95% CI 2.88 to 4.30) and age (OR 1.04 95% CI 1.00 to 1.09) were associated with use of medications not recommended for pregnancy.

Conclusions: Women with type 2 diabetes have suboptimal contraceptive provision despite multiple exposures to medications not recommended for pregnancy. Regular assessment of contraceptive use, reproductive intentions, and medication review is urgently needed in primary care settings to minimize pregnancy-related risks.