Incidence Of Diabetes In Patients Research Articles

Increased risk of incident diabetes in patients with MAFLD not meeting the criteria for NAFLD

We aimed to compare the risk of incident diabetes according to fatty liver disease (FLD) definition, focusing on the comparison between those who met criteria for either metabolic dysfunction-associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD) but not the other. This was a 5.0-year (interquartile range, 2.4–8.2) retrospective longitudinal cohort study of 21,178 adults who underwent at least two serial health checkup examinations. The presence of hepatic steatosis was determined by abdominal ultrasonography at the first health examination. Cox proportional hazard analyses were used to compare the risk of incident diabetes among five groups. Incident diabetes cases occurred in 1296 participants (6.1%). When non-FLD without metabolic dysfunction (MD) group was set as a reference, the risk of incident diabetes increased in the order of NAFLD-only, non-FLD with MD, both FLD, and MAFLD-only groups. The presence of excessive alcohol consumption and/or hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, FLD, and MD synergistically increased the risk of incident diabetes. MAFLD-only group showed a greater increase in incidence of diabetes than non-FLD with MD and NAFLD-only groups. The interaction among excessive alcohol consumption, HBV/HCV infection, MD, and hepatic steatosis on the development of diabetes should not be overlooked.

Abstract #1402477: Sixth-Nerve Palsy in Uncontrolled Type 1 Diabetes with Insulin Dependence

Diabetic retinopathy is the most common and well-known ophthalmologic complications in diabetic patients. However, oculomotor palsy is one of the most frequent neuro-ophthalmologic complications of diabetic patients. Specifically, sixth nerve palsy is the most common, however infrequently studied. Our patient is a 51-year-old female with a past medical history of insulin-dependent diabetes mellitus, hypertension, chronic sinusitis, and chronic pain syndrome that presented with complaints of worsening headache and diplopia. Patient was hemodynamically stable on admission. Upon examination of the eye, the patient's right eye did not cross the midline in lateral gaze and was found to have diplopia in primary and lateral gaze of left eye. She was found to have recurrent sixth nerve palsy upon further evaluation of her visual deficit. Labs showed creatinine of 0.61 mg/dl (0.66-1.25 mg/dL), sodium of 129 mmol/L (135-145 mmol/L), potassium of 4.4 mmol/L (3.5-5.1 mmol/L), an anion gap of 2 mmol/L (3-13 mmol/L), blood glucose in the 300-400 mg/dL range (70-100 mg/dL) with most recent blood glucose of 168 mg/dL. Her hemoglobin A1C is 13.0 (< 6%). Her complete blood count shows a white blood cell count of 6,000/uL (3,600-10,700/uL) and a hemoglobin of 14 g/dL (13.0-18.0 g/dL). Magnetic resonance venography of the head was negative for cerebral venous sinus thrombosis and magnetic resonance imaging of the brain was negative for acute abnormalities. She was treated with basal insulin of 30 units nightly and bolus insulin of 3 units three times a day before meals for type 1 diabetes with hyperglycemia with long-term insulin use. Visual deficit was treated by observation by ophthalmology with symptomatic help through eyeglass prisms. She was discharged after one night of hospital stay with recommendations to control her home basal insulin with a carbohydrate-controlled bolus dose during meals. She was recommended to follow-up with endocrinology outpatient to discuss use of insulin pump to better control her diabetes. Sixth-nerve palsy is a frequent but lesser-known neuro-ophthalmologic complication of poorly controlled diabetic patients. Studies have shown a higher incidence of diabetes in patients with sixth-nerve palsy, warranting a more focused medical evaluation along with close observation and tighter control of blood glucose levels and hemoglobin A1C.

Abstract #1412731: Sixth-Nerve Palsy in a Patient with Type 1 Diabetes

Oculomotor palsy is one of the most frequent neuro-ophthalmologic complications in patients with diabetes. Specifically, sixth nerve palsy is the most common. A 51-year-old female with a past medical history of type 1 diabetes on insulin and hypertension presented with complaints of worsening headache and diplopia. Physical exam was remarkable for recurrent sixth nerve palsy. Patient was hemodynamically stable. Labs showed blood glucose of 367 mg/dL (70-100 mg/dL), an anion gap of 2 mmol/L (3-13 mmol/L), creatinine of 0.61 mg/dl (0.66-1.25 mg/dL), sodium of 129 mmol/L (135-145 mmol/L), and potassium of 4.4 mmol/L (3.5-5.1 mmol/L). Her hemoglobin A1C was 13.0% Her complete blood count shows a white blood cell count of 6,000/uL (3,600-10,700/uL) and a hemoglobin of 14 g/dL (13.0-18.0 g/dL). Magnetic resonance venography of the head was negative for cerebral venous sinus thrombosis and magnetic resonance imaging of the brain was negative for acute abnormalities. Blood glucose readings improved during hospitalization after optimizing her insulin regimen. She was recommended to follow-up with outpatient endocrinology to discuss use of insulin pump to better control her diabetes. Sixth-nerve palsy is a frequent but lesser-known neuro-ophthalmologic complication of poorly controlled diabetic patients. Studies have shown a higher incidence of diabetes in patients with sixth-nerve palsy, warranting a more focused medical evaluation along with close observation and tighter control of blood glucose levels and hemoglobin A1C.

Abstract #1413743: New Onset Diabetes and Acute Pancreatitis- A Sequela of Long COVID?

The association between worse COVID-19 outcomes and diabetes has been well-established in the literature. However, with more cases of new-onset diabetes and pancreatitis being reported with or after COVID-19 infection, it poses the question if there is a causal relationship between them. 31 y/o female with COVID-19 infection 4-6 weeks ago with moderate symptoms (not requiring hospital admission or monoclonal ab), presented to ED with bandlike epigastric pain radiating to back, which is worsened with food, associated with nausea, vomiting, polyuria, and fatigue. Workup showed lipase 232, AST 180, ALT 256. Blood glucose was 281 and HbA1c was 12. CT A/P showed post cholecystectomy status, normal pancreas with mesenteric adenitis. MRCP showed hepatic steatosis with trace fluid around the pancreas s/o inflammation, and no evidence of choledocholithiasis or biliary dilatation. She denied alcohol use and autoimmune workup for pancreatitis was unremarkable. Islet cell antibodies were negative. The patient improved with fluid resuscitation and was discharged home on insulin with plans to transition to oral agents outpatient. Long COVID is defined as a range of conditions or symptoms in patients recovering from COVID-19, lasting beyond 4 weeks after infection. A retrospective cohort study showed increased new-onset diabetes incidence in patients after COVID-19. This was redemonstrated in a systematic review and meta-analysis that showed a 14.4% increased proportion of new diagnoses of diabetes in patients hospitalized with COVID-19. Possible pathophysiology that have been attributed to this include undiagnosed pre-existing diabetes, hyperglycemia secondary to acute illness and stress from increased inflammatory markers during the cytokine storm, the effect of viral infections on the pancreas, and concurrent steroid use in patients with severe respiratory disease. The binding of SARS-CoV-2 to ACE2 receptors is thought to the other mechanism by which COVID can cause pancreatitis and hyperglycemia. Study showed increased lipase and amylase levels in patients with COVID and the increase in serum levels was proportional to the severity of the disease. Patients who died due to COVID-19 were also found to have degeneration of the islet cells. While, several studies have showed new onset diabetes and pancreatitis during an active COVID infections, we need larger cohort studies to comment on its true association or causation, especially in patients with long COVID symptoms. As more cases of new onset diabetes and pancreatitis with COVID-19 are being reported, there may be a need for more frequent blood sugar monitoring during the recovery phase of COVID-19.

Triglyceride glucose-body mass index and the risk of progression to diabetes from prediabetes: A 5-year cohort study in Chinese adults.

Evidence regarding the relationship between the triglyceride glucose-body mass index (TyG-BMI) and the risk of progression from prediabetes to diabetes remains limited. Our study aimed to investigate the relationship between them in patients with prediabetes. In this retrospective cohort study, data were collected from 25,279 patients with prediabetes who received health checks between 2010 and 2016. We used a Cox proportional-hazards regression model to examine the relationship between TyG-BMI and diabetes risk. We used Cox proportional hazards regression with cubic spline functions and smooth curve fitting to identify the nonlinear relationship between them. In addition, A series of sensitivity and subgroup analyses were also conducted. The mean age of the included participants was 49.29 ± 13.82 years old, and 1,6734 (66.2%) were male. The mean TyG-BMI was 219.47. The median follow-up time was 2.89 years, and 2,687 (10.63%) individuals had a final diagnosis of diabetes. After adjusting for covariates, TyG-BMI was positively linked with incident diabetes in patients with prediabetes (HR = 1.011, 95%CI 1.010-1.012). TyG-BMI had a non-linear connection with diabetes risk, and its inflection point was 231.66. Right and left effects sizes (HR) at the inflection point were 1.017 (95%CI:1.014-1.019) and 1.007 (95%CI:1.005-1.009), respectively. The sensitivity analysis demonstrated the robustness of these results. This study demonstrated a positive, non-linear relationship between the TyG-BMI and diabetes risk in Chinese patients with prediabetes. When the TyG-BMI was <231.66, there was a significant positive association between TyG-BMI and the risk of progression from prediabetes to diabetes. This study serves as a reference to promote clinical consultation and optimize diabetes prevention decisions for patients with prediabetes.

Diabetes and Obesity in Down Syndrome Across the Lifespan: A Retrospective Cohort Study Using U.K. Electronic Health Records.

Down syndrome (DS) is the most common form of chromosomal trisomy. Genetic factors in DS may increase the risk for diabetes. This study aimed to determine whether DS is associated with an increased incidence of diabetes and the relationship with obesity across the life span compared with control patients. This matched population-based cohort study analyzed UK Clinical Practice Research Datalink data from 1990 to 2020. A total of 9,917 patients with DS and 38,266 control patients were analyzed. Diabetes rates were higher in patients with DS (incidence rate ratio 3.67; 95% CI 2.43-5.55; P < 0.0001) and peaked at a younger age (median age at diagnosis 38 [interquartile range 28-49] years vs. 53 [43-61] years in control patients). Incidence rates (per 1,000 person-years) for type 1 diabetes mellitus were 0.44 (95% CI 0.31-0.61) in patients with DS vs. 0.13 (0.09-0.17) in control patients. Type 2 diabetes mellitus (T2DM) rates were higher in patients with DS versus control patients in age-groups from 5 years up to 34 years. In patients with DS, peak mean BMI was higher and at a younger age (males 31.2 kg/m2 at age 31 years; females 32.1 kg/m2 at 43 years) versus control patients (males 29.5 kg/m2 at 54 years; females 29.2 kg/m2 at 51 years). Obesity was associated with an increased incidence of T2DM. At younger ages, the incidence of diabetes in patients with DS is up to four times that of control patients. Peak mean BMI is higher and established earlier in DS, contributing to T2DM risk. Further investigation into the relationship between obesity and diabetes in DS is required to inform treatment and prevention measures.

The Association Between the Triglyceride-to-High-Density Lipoprotein Cholesterol Ratio and the Risk of Progression to Diabetes From Prediabetes: A 5-year Cohort Study in Chinese Adults.

ObjectiveEvidence regarding the relationship between the triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-c) ratio and the risk of progression from prediabetes to diabetes remains limited. The purpose of our study was to investigate the relationship between the TG/HDL-C ratio and incident diabetes in prediabetic patients.MethodsThis retrospective cohort study covered 32 regions and 11 cities in China and consecutively and non-selectively collected data from 15,017 patients with prediabetes who had received a health check from 2010 to 2016. Data were obtained from the DATADRYAD database (www.datadryad.org). The Cox proportional-hazards regression model with cubic spline functions and smooth curve fitting (cubic spline smoothing) was used to explore the non-linear relationship between the baseline TG/HDL-c ratio and the risk of diabetes in patients with prediabetes. In addition, we performed a series of sensitivity and subgroup analyses.ResultsThe mean age of the included individuals was 50.95 ± 13.48 years, and 9,745 (64.51%) were men. The median (interquartile range) TG/HDL-c ratio was 1.09 (0.69–1.72). During a median follow-up time of 3.05 years, 1,731 (11.46%) patients had a final diagnosis of diabetes. The analysis after adjusting for covariates showed that the TG/HDL-c ratio was positively related to incident diabetes in patients with prediabetes (HR = 1.111, 95% CI 1.061–1.164). Participants with the highest TG/HDL-c ratio (Q4) had higher diabetes incidence rates than those with the lowest TG/HDL-c ratio (Q1) (P < 0.001 for the trend). There was a non-linear relationship between the TG/HDL-c ratio and the risk of diabetes, and the inflection point of the TG/HDL-c ratio was 1.415. The effect sizes (HR) on the left and right sides of the inflection point were 1.336 (95% CI: 1.134–1.573) and 1.055 (95% CI: 0.988–1.126), respectively. The sensitivity analysis demonstrated the robustness of these results.ConclusionThis study demonstrates a positive, non-linear relationship between the TG/HDL-c ratio and the risk of diabetes in Chinese patients with prediabetes. Aggressive intervention from a treatment perspective is required to lower the TG/HDL-c ratio below the inflection point (1.415) by lowering TG or increasing HDL-c levels.

β-cell function and insulin sensitivity contributions on incident diabetes in patients with endogenous Cushing’s syndrome

ObjectiveTo evaluate the relative contributions of β-cell function and insulin sensitivity on the deterioration of glucose tolerance from OGTT in patients with endogenous CS. MethodsWe retrospectively analyzed the data of 60 patients with CS and determined the glucose metabolism and β-cell function through OGTT. Their general characteristics were retrieved. A series of parameters for assessing insulin sensitivity and β-cell function was calculated. The logistic regression model was used to investigate insulin sensitivity and β-cell function contributions on incident diabetes. ResultsOf the 60 patients with CS, 10 (16.7%), 21 (35%), and 29 (48.3%) were classified as CS/ normal glucose tolerance (NGT), CS/prediabetes, and CS/diabetes mellitus (DM). Compared with the HCs, the CS/NGT patients had higher HOMA-IR and lower ISI-Matsuda but with a compensatory increase in HOMA-β. Significant decreasing trends were observed in HOMA-β, AUCI/G and ΔI30/ΔG30 among CS/NGT, CS/prediabetes and CD/DM groups. The OR of incident diabetes compared with the high AUCI/G/high ISI group was significant in the low AUCI/G/high ISI group. ConclusionImpairment of the β-cell function had a more profound effect on incident diabetes than decreased insulin sensitivity. An approach based on an OGTT has utility for diagnosing dysglycaemia and β-cell dysfunction in patients with CS.

Risk of incident type 2 diabetes in patients with psoriatic arthritis: A systematic review and meta-analysis of cohort studies.

To determine the risk of type 2 diabetes among patients with psoriatic arthritis (PsA). Electronic database searches of PubMed, EMBASE and Cochrane Library were performed from inception to June 2020 and updated in May 2022. Cohort studies were included if they reported hazard ratios (HR) or relative risks with 95% confidence interval (CI) of incident diabetes in patients with PsA compared with non-rheumatic populations. Pooled HR and 95% CI were calculated using a DerSimonian and Laird method random-effects model. A total of 5 studies comprising 37 811 PsA patients with 174 825 patient-years and 476 838 non-rheumatic controls with 2 945 358 patient-years were identified and included in our data analysis. During the follow-up, 2335 and 23 035 incident diabetes were observed in PsA and non-rheumatic control groups, corresponding to a crude incidence rate of 13.4 and 7.8 per 1000 patient-years, respectively. The pooled age- and gender-adjusted, and fully adjusted HR of incident diabetes in patients with PsA compared with non-rheumatic populations were 1.54 (95% CI: 1.43-1.67, I2 = 50.8%) and 1.38 (95% CI: 1.31-1.47, I2 = 0.0%), respectively. Our study indicates a 38% increase in the risk of type 2 diabetes among patients with PsA, with an incidence rate of 13.4 per 1000 patients-years. These findings suggest the awareness of managing diabetes with careful screening of PsA patients in daily practice.

Increased risk of incident diabetes in patients with long COVID.

Increased risk of incident diabetes in patients with long COVID.

The Long-Term Effects of Non-Pharmacological Interventions on Diabetes and Chronic Complication Outcomes in Patients With Hyperglycemia: A Systematic Review and Meta-Analysis.

ObjectiveThis study aimed at examining the long-term effects of non-pharmacological interventions on reducing the diabetes incidence among patients with prediabetes and chronic complications events among patients with hyperglycemia (pre-diabetes and diabetes) by performing a systematic review and meta-analysis of randomized controlled trials (RCTs).MethodsPubMed, MEDLINE, EMBASE, the Cochrane Library, and the Web of Science Core Collection were searched for studies published between January 1990 and November 2021, looking for RCTs to evaluate the effects of non-pharmacological interventions on preventing the incidence of diabetes and chronic complications in comparison with medical therapy, placebo, or usual diabetes care. Two independent reviews extracted relevant data and quality assessment. Any discrepancies were resolved by a third reviewer.ResultsIn total, 20 articles involved 16 RCTs (follow-up ranged from 2 to 30 years) were included. Pooled analysis of intervention studies demonstrated clearly that non-pharmacological interventions have a significant effect on reducing the diabetes events in patients with prediabetes (RR 0.62; 95% CI 0.54, 0.71). Pooled analysis of extended follow-up studies showed that non-pharmacological interventions could effectively reduce the diabetes incidence in patients with prediabetes (RR 0.78; 95% CI 0.63, 0.96). Meta-regression and subgroup analysis indicates that the diabetes incidence of the long-term group (duration > 3 years) was clearly reduced by 0.05% compared with the relatively short-term group (duration ≤ 3 years). The incidence of microvascular complications in patients with hyperglycemia was effectively lowered by non-pharmacological interventions (RR 0.60; 95% CI 0.43, 0.83).ConclusionNon-pharmacological interventions have a long-term effect on reducing the diabetes incidence among prediabetic patients and effectively preventing microvascular complications on hyperglycemia.Systematic Review Registration https://www.crd.york.ac.uk/prospero/.

Impact of IL-28B gene polymorphism on chronic hepatitis-C patients progression with diabetes and non-diabetes

BackgroundChronic hepatitis C (CHC) is a silent viral infection; however, elevated mortality and morbidity rates are noted in Egypt due to its adverse effects. The augmented incidence of diabetes in patients with viral C infection may be owing to glucose intolerance, high BMI, senility, and inherited factors.Purpose of the studyLittle information is available about the connection between interleukin-28B (IL-28B) genotype in disease progression among CHC patients with diabetes. Thus, we aimed to assess the association between IL-28B genotype (rs12979860) in CHC with type 2 diabetes mellitus (T2DM) versus those without diabetes in disease progression among Egyptian patients.ResultsCC genotype was significantly lower in diabetics than in non-diabetics (13.7% vs. 36.3%). While (CT/TT) were significantly higher in diabetics than in non-diabetics (CT 58.8% vs. 43.7%), (TT 27.5% vs. 20%) (p = 0.03) and likewise alleles (p = 0.04). Multivariate logistic regression analysis was significant with viral load p < 0.001, alanine aminotransferase (ALT) p < 0.001, genotype CC versus TT p = 0.04 & T2DM p = 0.03.ConclusionCC genotype might be used as a protective factor and TT genotype as a risk factor in disease progression among CHC patients with T2DM. Additionally, viral load, ALT & T2DM might interplay as predictors of disease severity. Detecting the genetic factors can be helpful in predicting and preventing the complications of diabetes associated with the hepatitis C virus (HCV).

Pharmacokinetics of metformin in collagen-induced arthritis rats

Due to the elevated presence of cytokines, the expressions of metabolic enzymes and drug transporters are altered in rheumatoid arthritis (RA). Given the high incidence of diabetes in patients with RA, the aim of the present study was to investigate the metformin pharmacokinetics of a single oral dose in rats with collagen-induced arthritis (CIA). Blood and urine samples were collected at different timepoints, and analyzed by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Tissue samples were also collected to investigate the expression of metabolic enzymes and drug transporters by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blot. The results indicated that the bioavailability of metformin was markedly decreased in the CIA rats. Moreover, metformin was not metabolized by enzymes of rat liver microsomes, suggesting that the decreased bioavailability of metformin was independent of the liver metabolism. In addition, the mRNA, protein expression level and activity of the renal organic cation transporter 2 (OCT2) was markedly increased, suggesting that the enhanced renal clearance of metformin in CIA rats may be due to the up-regulated activity of OCT2. In conclusion, our study suggested that the reduced bioavailability of metformin in CIA rats is possibly related to the up-regulated function of the renal protein OCT2.

The association between the biological disease-modifying anti-rheumatic drugs and the incidence of diabetes: A systematic review and meta-analysis

Whether the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) would influence the risk of new-onset diabetes remains uncertain. Therefore, we performed a systematic review and meta-analysis to evaluate the association between the use of bDMARDs and the incidence of diabetes in patients with systemic inflammatory conditions. Pubmed, Medline, Embase and the Cochrane Central Register of Controlled Trials were searched for studies published from January 2000 to March 2020. Studies conducted in systemic inflammatory conditions with reports of the incidence of diabetes in subjects treated with bDMARDs were included. With 22 randomized controlled trials and 3 cohort studies included, the overall result indicated that compared with non-bDMARD treatment, the use of bDMARDs was significantly associated with decreased incidence of diabetes in patients with systemic inflammatory conditions (RR = 0.56, 95 % CI, 0.43 to 0.74, P < 0.001, I2 = 69 %), especially in patients with in rheumatoid arthritis (RR = 0.54, 95 % CI, 0.38 to 0.76, P = 0.0005, I2 = 26). Reduced risk of new-onset diabetes was observed in studies with follow-up more than 1 year (RR = 0.73, 95 % CI, 0.54 to 0.99, P = 0.04, I2 = 88). New-onset diabetes was less frequent in patients with TNF-α inhibitor treatment (RR = 0.54, 95 % CI, 0.48 to 0.60, P < 0.001, I2 = 42 %) and abatacept treatment (RR = 0.44, 95 % CI, 0.34 to 0.58, P < 0.001, I2 = 3 %), which might be associated with the inhibition of TNF-α mediated inflammatory responses and dysregulated T cell activation and immune responses respectively. Further investigations are required to validate the glucose metabolism protective effect of bDMARDs and clarify the underlying mechanisms of the crosstalk between bDMARDs and diabetes.

Apolipoprotein M and Sphingosine-1-Phosphate: A Potentially Antidiabetic Tandem Carried by HDL.

The frequent finding of low HDL cholesterol in patients with type 2 diabetes (T2D) or at increased risk for T2D has been traditionally interpreted as the consequence of hypertriglyceridemia and hyperacylemia, which are caused by insulin resistance and hyperinsulinemia (1). However, several observations also point to antidiabetic actions of HDL (1,2). Post hoc analyses of randomized controlled trials showed that inhibitors of cholesteryl ester transfer protein, which increase HDL cholesterol by 25 to 100%, improve the glycemic control of subjects with diabetes and lower the incidence of diabetes in patients who are treated with statins (3). Infusion of artificial reconstituted HDL led to acute decreases in glucose levels and improved insulin sensitivity in subjects with diabetes (4). Mendelian randomization studies generated controversial data, with one study supporting and another disproving genetic causality of HDL for T2D (5,6). Data from genetic mouse models indicate that HDL secures both insulin production in pancreatic β-cells and insulin action in the periphery (2). The clinical exploitation of HDL in the prevention and management of diabetes—for example, the development of drugs that stimulate or mimic the antidiabetic effects of HDL or biomarkers that improve risk prediction—is hampered by the presence of hundreds of different proteins and lipid species in HDL, several of which show antidiabetic properties (7). In this issue of Diabetes , Kurano et al. (8) provide evidence that at least a part of HDL’s antidiabetic action involves apolipoprotein M (apoM) and its lipid ligand sphingosine-1-phosphate (S1P), two quantitatively minor components of HDL. S1P is the …

Dalcetrapib Reduces Risk of New-Onset Diabetes in Patients With Coronary Heart Disease.

OBJECTIVEIncident type 2 diabetes is common among patients with recent acute coronary syndrome and is associated with an adverse prognosis. Some data suggest that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes. We compared the effect of treatment with the CETP inhibitor dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome.RESEARCH DESIGN AND METHODSIn the dal-OUTCOMES trial, 15,871 patients were randomly assigned to treatment with dalcetrapib 600 mg daily or placebo, beginning 4–12 weeks after an acute coronary syndrome. Absence of diabetes at baseline was based on medical history, no use of antihyperglycemic medication, and hemoglobin A1c and serum glucose levels below diagnostic thresholds. Among these patients, incident diabetes after randomization was defined by any diabetes-related adverse event, new use of antihyperglycemic medication, hemoglobin A1c ≥6.5%, or a combination of at least two measurements of serum glucose ≥7.0 mmol/L (fasting) or ≥11.1 mmol/L (random).RESULTSAt baseline, 10,645 patients (67% of the trial cohort) did not have diabetes. During a median follow-up of 30 months, incident diabetes was identified in 403 of 5,326 patients (7.6%) assigned to dalcetrapib and in 516 of 5,319 (9.7%) assigned to placebo, corresponding to absolute risk reduction of 2.1%, hazard ratio of 0.77 (95% CI 0.68–0.88; P < 0.001), and a need to treat 40 patients for 3 years to prevent 1 incident case of diabetes. Considering only those with prediabetes at baseline, the number needed to treat for 3 years to prevent 1 incident case of diabetes was 25. Dalcetrapib also decreased the number of patients who progressed from normoglycemia to prediabetes and increased the number who regressed from diabetes to no diabetes.CONCLUSIONSIn patients with a recent acute coronary syndrome, incident diabetes is common and is reduced substantially by treatment with dalcetrapib.

P6193Dalcetrapib reduces incident diabetes in patients with recent acute coronary syndrome

Abstract Background Among patients with acute coronary syndrome (ACS) who do not have diabetes, incident diabetes is common and associated with an adverse prognosis. Some data suggest that high density lipoprotein (HDL) has favourable effects on beta cell function and that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes in conjunction with increased HDL cholesterol (HDL-C) concentration. Dalcetrapib is a CETP inhibitor under ongoing evaluation as a potential cardiovascular therapy. Purpose We compared the effect of treatment with dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome (ACS). Methods In the dal-OUTCOMES trial, 15,871 patients were randomly assigned to treatment with dalcetrapib 600 mg or placebo daily, beginning 4–12 weeks after ACS. Absence of diabetes at baseline was based upon medical history, no use of diabetes medication, haemoglobin A1c &lt;6.5%, and plasma glucose level &lt;7 mmol/L (if measured under fasting conditions) or &lt;11.1 mmol/L (if measured under non-fasting conditions). Among these patients, incident diabetes after randomization was defined by any diabetes-related adverse event, use of a diabetes medication, HbA1c ≥6.5%, or two measurements of plasma glucose ≥7 mmol/L (fasting) or ≥11.1 mmol/L (non-fasting). The association of incident diabetes with baseline and on-treatment HDL-C was determined. Results At baseline, 10621 patients (67% of the trial cohort) did not have diabetes and formed the analysis cohort. Over median follow-up of 31 months, incident diabetes was identified in 392 of 5314 patients (7.4%) assigned to dalcetrapib and 505 of 5307 (9.5%) assigned to placebo (odds ratio [OR] 0.76; 95% confidence interval [CI] 0.66–0.87; P&lt;0.001). This corresponds to an absolute reduction in incident diabetes of 2.1%, and a need to treat 47 patients (for 31 months) to prevent 1 case of diabetes. Kaplan-Meier estimates of the cumulative incidence of diabetes are shown in the Figure. Across both treatment groups, incident diabetes was inversely associated with baseline HDL-C (OR 0.98 for 1 mg/dL increase in baseline HDL-C; 95% CI 0.97–0.98, P&lt;0.001). In the dalcetrapib group, there was a further inverse association of incident diabetes with the change in HDL-C on assigned treatment (OR 0.98 for 1 mg/dL increase in HDL-C from baseline; 95% CI 0.97–0.99, P=0.002). Dalcetrapib was safe and generally well-tolerated in the trial. Conclusions In patients with recent ACS who do not have diabetes at baseline, incident diabetes is common. Dalcetrapib treatment reduced the relative risk of incident diabetes by 24% and the absolute risk by 2.1% over a median of 31 months. The reduction in incident diabetes with dalcetrapib was associated with increased HDL-C on treatment. Acknowledgement/Funding The dal-OUTCOMES trial was funded by F. Hoffmann LaRoche

Metabolically Healthy Obesity And Risk Of Incident Diabetes In Patients Treated With Statins

Metabolically Healthy Obesity And Risk Of Incident Diabetes In Patients Treated With Statins

Type 2 diabetes and Parkinson's disease

Type 2 diabetes and Parkinson's disease

Hepatic transcriptomic signatures of statin treatment are associated with impaired glucose homeostasis in severely obese patients

BackgroundClinical data identified an association between the use of HMG-CoA reductase inhibitors (statins) and incident diabetes in patients with underlying diabetes risk factors such as obesity, hypertension and dyslipidemia. The molecular mechanisms however are unknown.MethodsAn observational cross-sectional study included 910 severely obese patients, mean (SD) body mass index (BMI) 46.7 (8.7), treated with or without statins (ABOS cohort: a biological atlas of severe obesity). Data and sample collection took place in France between 2006 and 2016. Transcriptomic signatures of statin treatment in human liver obtained from genome-wide transcriptomic profiling of five different statin drugs using microarrays were correlated to clinico-biological phenotypes and also assigned to biological pathways and mechanisms. Patients from the non-statin-users group were matched to patients in the statin users group by propensity score analysis to minimize confounding effects from age, gender, parental familial history of diabetes, BMI, waist circumference, systolic and diastolic blood pressure and use of anti-hypertensive drugs as pre-specified covariates.ResultsWe determined the hepatic, statin-related gene signature from genome-wide transcriptomic profiling in severely obese patients with varying degrees of glucose tolerance and cardio-metabolic comorbidities. One hundred and fifty seven patients on statin treatment in the matched cohort showed higher diabetes prevalence (OR = 2.67; 95%CI, 1.60–4.45; P = 0.0002) and impairment of glucose homeostasis. This phenotype was associated with molecular signatures of increased hepatic de novo lipogenesis (DNL) via activation of sterol regulatory element-binding protein 1 (SREBP1) and concomitant upregulation of the expression of key genes in both fatty acid and triglyceride metabolism.ConclusionsA DNL gene activation profile in response to statins is associated with insulin resistance and the diabetic status of the patients. Identified molecular signatures thus suggest that statin treatment increases the risk for diabetes in humans at least in part via induction of DNL.Trial registrationNCT01129297. Registered May 242,010 (retrospectively registered).