It remains unclear whether an increased progression rate of chronic kidney disease (CKD) adds predictive information regarding cardiovascular disease (CVD) risk. The aim of this study was to evaluate ...the association between CKD progression, based on estimated glomerular filtration rate (eGFR) slope estimates and the risk for CVD.
We compared the updated eGFR slope calculated over multiple overlapping 2-year periods and the updated mean eGFR. Incident CKD subjects were selected from a prevalent population with diabetes (T2DM). Subjects from the UK Clinical Practice Research Data Link GOLD (CPRD) were followed from CKD diagnosis (n = 30,222) until heart failure (HF), myocardial infarction (MI), ischemic stroke (IS), or a composite end point including all 3 event types (MACE plus), mortality, database dropout, or end of study follow-up.
Both the updated eGFR slope and updated mean eGFR were associated with MACE plus and HF. Updated eGFR slope decline of > –3 ml/min/1.73 m2 increased the risk for MACE plus (adjusted hazard ratio HR = 1.45; 95% confidence interval CI, 1.26–1.67), HF (HR = 1.50; 95% CI, 1.27–1.76), and MI (HR = 1.39; 95% CI, 1.01–1.91).
This study strongly supports current evidence that CKD is an independent risk factor for CVD. From a clinical perspective, both rate of progression and cumulative status of CKD describe distinct aspects of the cardiorenal risk among persons with diabetes. This evidence is essential to enable more timely and improved use of treatments in this population.
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IntroductionIn type 1 diabetes, potential loss of life-years is greatest in those who are youngest at the time of onset. Using data from a nationwide cohort of patients with type 1 diabetes, we aimed ...to study risk factor trajectories by age at diagnosis.Research design and methodsWe stratified 30 005 patients with type 1 diabetes aged 18–75 years into categories based on age at onset: 0–10, 11–15, 16–20, 21–25, and 26–30 years. HbA1c, albuminuria, estimated glomerular filtration rate (eGFR), body mass index (BMI), low-denisty lipoprotein (LDL)-cholesterol, systolic blood pressure (SBP), and diastolic blood pressure trends were analyzed using mixed models. Variable importance for baseline HbA1c was analyzed using conditional random forest and gradient boosting machine approaches.ResultsIndividuals aged ≥16 years at onset displayed a relatively low mean HbA1c level (~55–57 mmol/mol) that gradually increased. In contrast, individuals diagnosed at ≤15 years old entered adulthood with a mean HbA1c of approximately 70 mmol/mol. For all groups, HbA1c levels stabilized at a mean of approximately 65 mmol/mol by about 40 years old. In patients who were young at the time of onset, albuminuria appeared at an earlier age, suggesting a more rapid decrease in eGFR, while there were no distinct differences in BMI, SBP, and LDL-cholesterol trajectories between groups. Low education, higher age, and poor risk factor control were associated with higher HbA1c levels.ConclusionsYoung age at the diabetes onset plays a substantial role in subsequent glycemic control and the presence of albuminuria, where patients with early onset may accrue a substantial glycemic load during this period.
IntroductionEvidence on the effects of structured nutrition education is weak in adults with type 1 diabetes mellitus (T1D) with moderately impaired glycemic control. Objective was to compare the ...effects of different types of nutrition education programs on glycemic control, cardiovascular risk factors, quality of life, diet quality and food choices in T1D.Research design and methodsA 12 months randomized controlled study conducted at nine diabetes specialist centers with three parallel arms: (i) a food-based approach (FBA) including foods with low glycemic index or (ii) carbohydrate counting (CC) according to today’s standard practice or (iii) individual sessions according to routine care (RC). The primary end point was difference in glycated hemoglobin A1c (HbA1c) between groups at 12 months.Results159 patients were randomized (FBA: 51; CC: 52; RC: 55). Mean (SD) age 48.6 (12.0) years, 57.9% females and mean (SD) HbA1c level 63.9 (7.9) mmol/mol, 8% (0.7%). After 3 months, HbA1c improved in both FBA and CC compared with RC. However, there were no significant differences at 12 months in HbA1c; FBA versus RC (−0.4 mmol/mol (1.3), 0.04% (0.1%)), CC versus RC (−0.8 mmol/mol (1.2), 0.1% (0.1%)), FBA versus CC (0.4 mmol/mol (0.3), 0.04% (0.01%)). At 12 months, intake of legumes, nuts and vegetables was improved in FBA versus CC and RC. FBA also reported higher intake of monounsaturated and polyunsaturated fats compared with RC, and dietary fiber, monounsaturated and polyunsaturated fats compared with CC (all p values <0.05). There were no differences in blood pressure levels, lipids, body weight or quality of life.ConclusionsNutrition education using an FBA, CC or RC is equivalent in terms of HbA1c and cardiovascular risk factors in persons with T1D with moderately impaired glycemic control. An FBA had benefits regarding food choices compared with CC and RC.
Although prior research has identified multiple risk factors for diabetic ketoacidosis (DKA), clinicians continue to lack clinic-ready models to predict dangerous and costly episodes of DKA. We asked ...whether we could apply deep learning, specifically the use of a long short-term memory (LSTM) model, to accurately predict the 180-day risk of DKA-related hospitalization for youth with type 1 diabetes (T1D).
We aimed to describe the development of an LSTM model to predict the 180-day risk of DKA-related hospitalization for youth with T1D.
We used 17 consecutive calendar quarters of clinical data (January 10, 2016, to March 18, 2020) for 1745 youths aged 8 to 18 years with T1D from a pediatric diabetes clinic network in the Midwestern United States. The input data included demographics, discrete clinical observations (laboratory results, vital signs, anthropometric measures, diagnosis, and procedure codes), medications, visit counts by type of encounter, number of historic DKA episodes, number of days since last DKA admission, patient-reported outcomes (answers to clinic intake questions), and data features derived from diabetes- and nondiabetes-related clinical notes via natural language processing. We trained the model using input data from quarters 1 to 7 (n=1377), validated it using input from quarters 3 to 9 in a partial out-of-sample (OOS-P; n=1505) cohort, and further validated it in a full out-of-sample (OOS-F; n=354) cohort with input from quarters 10 to 15.
DKA admissions occurred at a rate of 5% per 180-days in both out-of-sample cohorts. In the OOS-P and OOS-F cohorts, the median age was 13.7 (IQR 11.3-15.8) years and 13.1 (IQR 10.7-15.5) years; median glycated hemoglobin levels at enrollment were 8.6% (IQR 7.6%-9.8%) and 8.1% (IQR 6.9%-9.5%); recall was 33% (26/80) and 50% (9/18) for the top-ranked 5% of youth with T1D; and 14.15% (213/1505) and 12.7% (45/354) had prior DKA admissions (after the T1D diagnosis), respectively. For lists rank ordered by the probability of hospitalization, precision increased from 33% to 56% to 100% for positions 1 to 80, 1 to 25, and 1 to 10 in the OOS-P cohort and from 50% to 60% to 80% for positions 1 to 18, 1 to 10, and 1 to 5 in the OOS-F cohort, respectively.
The proposed LSTM model for predicting 180-day DKA-related hospitalization was valid in this sample. Future research should evaluate model validity in multiple populations and settings to account for health inequities that may be present in different segments of the population (eg, racially or socioeconomically diverse cohorts). Rank ordering youth by probability of DKA-related hospitalization will allow clinics to identify the most at-risk youth. The clinical implication of this is that clinics may then create and evaluate novel preventive interventions based on available resources.
Background Patients with diabetes mellitus (DM) experience higher rates of in-stent restenosis and greater benefit from drug-eluting stents implant at the time of percutaneous coronary intervention ...(PCI), necessitating prolonged dual anti-platelet therapy (DAPT). While DAPT reduces risk of ischemic events post-PCI, it also increases risk of bleeding. Whether bleeding rates differ among patients with and without DM, receiving long-term DAPT is unknown. Methods Among patients who underwent PCI and were maintained on DAPT for 1 year in a multicenter US registry, we assessed patient-reported bleeding over one year following PCI in patients with and without DM. Multivariable, hierarchical Poisson regression was used to evaluate the association of DM with bleeding during follow-up. Results Among 2334 PCI patients from 10 US hospitals (mean age 64, 54% ACS), 32.6% had DM. In unadjusted analyses, patients with DM had fewer bleeding events over the year following PCI (DM vs no DM: BARC = 1: 78.0% vs 87.7%, P < .001; BARC ≥2: 4.3% vs 5.3%, P = .33). Following adjustment, patients with (vs without DM) had a lower risk of BARC ≥1 bleeding during follow-up (relative risk RR 0.89, 95% CI 0.83–0.96). This decreased bleeding risk persisted after removing bruising from the endpoint definition. Conclusions In a real-world PCI registry, patients with DM experienced lower risk of bleeding risk on DAPT. As patients with DM also derive greater ischemic benefit from drug-eluting stents, which requires prolonged DAPT, our findings suggest that the balance between benefit and risk of this therapeutic approach may be even more favorable in patients with DM than previously considered.
Introduction: Corticoid therapy is well-known to improve the symptoms of psoriasis. Addison’s disease is an autoimmune disease which leads to a loss of cortisol production in the adrenal glands. This ...case report describes a patient with wide-spread psoriasis for 34 years who was cured when Addison’s disease was detected and substitution to reach normal biological cortisol levels was introduced. Case Report: A 59-year-old man was diagnosed with Addison’s disease. He had been tired for several years and had had difficulties in continuing his work. His brother had Addison’s disease and recommended him to make a screen for the disease. Synacthen test diagnosed Addison’s disease with a clear deficiency of cortisol production. After substitution with hydrocortisone the patient’s constitution improved rapidly and he felt no longer tired during work. At the same time, all skin lesions of psoriasis disappeared as well as aches in several joints, both symptoms having been present for a couple of decades. Previously, salves of cortisol had been used to reduce the symptoms of psoriasis, but now, 1–2 years later, after the treatment of Addison’s disease, no symptoms in the skin or joints have reoccurred. Conclusions: This report illustrates that Addison’s disease, although a rare condition, should be kept in mind before treatment of psoriasis is started. Especially if other symptoms such as fatigue are present, a screening test of serum cortisol in the morning should be liberally made. The report also illustrates a need of examining corticoid levels in patients with psoriasis compared to the general population.
To compare the effect of glucose-lowering drugs on peripheral nerve and kidney function in prediabetes.
Multicenter, randomized, placebo-controlled trial in 658 adults with prediabetes treated for 1 ...year with metformin, linagliptin, their combination or placebo. Endpoints are small fiber peripheral neuropathy (SFPN) risk estimated by foot electrochemical skin conductance (FESC < 70 μSiemens) and estimated glomerular filtration rate (eGFR).
Compared to the placebo, the proportion of SFPN was reduced by 25.1% (95% CI:16.3-33.9) with metformin alone, by 17.3% (95% CI 7.4-27.2) with linagliptin alone, and by 19.5% (95% CI 10.1-29.0) with the combination linagliptin/metformin (
< 0.0001 for all comparisons). eGFR remained +3.3 mL/min (95% CI: 0.38-6.22) higher with the combination linagliptin/metformin than with the placebo (
= 0.03). Fasting plasma glucose (FPG) decreased more with metformin monotherapy -0.3 mmol/L (95%CI: -0.48; 0.12,
= 0.0009) and with the combination metformin/linagliptin -0.2 mmol/L (95% CI: -0.37; -0.03) than with the placebo (
= 0.0219). Body weight (BW) decreased by -2.0 kg (95% CI: -5.65; -1.65,
= 0.0006) with metformin monotherapy, and by -1.9 kg (95% CI: -3.02; -0.97) with the combination metformin/linagliptin as compared to the placebo (
= 0.0002).
in people with prediabetes, a 1 year treatment with metformin and linagliptin, combined or in monotherapy, was associated with a lower risk of SFPN, and with a lower decrease in eGFR, than treatment with placebo.
Introduction and Objective: Although there is extensive knowledge of metabolic and cardiovascular effects of GLP-1 analogues, placebo-controlled trials are sparse examining how endogenous incretins ...are affected during therapy. The aim of this study was to evaluate the concentrations of GLP-1, GIP and glucagon in liraglutide treated persons with type 2 diabetes (T2D) and associations with changes in glycemic control. Methods: The current analysis included 106 patients with available biobank samples of the 124 persons with T2D who took part in the double-blind placebo-controlled MDI liraglutide trial. Differences in GLP-1, GIP and glucagon between treatment groups were evaluated using analysis of covariance, adjusting for baseline values. Linear regression was used to evaluate baseline concentrations of GLP-1, GIP, and glucagon as possible predictors for a greater or smaller treatment effect of liraglutide on HbA1c. Results: At 12 weeks GLP-1 was 25% lower (95% CI 9-37%, p=0.003) and GIP 39% higher (95% CI 8-79%, p=0.012) in the liraglutide group compared to the placebo group. At 24 weeks differences were sustained. Glucagon was lower in the liraglutide group at 12 weeks (p=0.052) but reached similar levels as the placebo group after 24 weeks (p=0.98). In the liraglutide group mean Hba1c decreased from 9.0% to 7.4%. Each 30% decrease in glucagon concentration at baseline was associated with 0.3% greater reduction in HbA1c at 24 weeks of treatment with liraglutide compared to placebo (95% CI 0.1-0.5%, p=0.001). Conclusion: An essential mechanism of metabolic effects of GLP-1 analogues is potentially mediated via increased GIP levels in persons with T2D. According to our findings serum glucagon levels may be an important biomarker for GLP-1 analogue responders. Disclosure M. Koci: None. I.B. Hirsch: Advisory Panel; Abbott. Research Support; Dexcom, Inc. Advisory Panel; Roche Diabetes Care. Research Support; MannKind Corporation, Tandem Diabetes Care, Inc. Advisory Panel; embecta. Research Support; Tandem Diabetes Care, Inc. Advisory Panel; Vertex Pharmaceuticals Incorporated. S. Seyed Ahmadi: None. M. Lind: Consultant; AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company. Research Support; Eli Lilly and Company. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Nordic InfuCare.
AbstractObjectiveTo evaluate if the lowest target level for glycated haemoglobin (HbA1c) of <6.5% is associated with lower risk for retinopathy and nephropathy than less tight control in children and ...adults with type 1 diabetes.DesignPopulation based cohort study.SettingSwedish National Diabetes Registry, 1 January 1998 to 31 December 2017.Participants10 398 children and adults with type 1 diabetes followed from diagnosis, or close thereafter, until end of 2017.Main outcome measuresRelative risk (odds ratios) for retinopathy and nephropathy for different mean levels of HbA1c.ResultsMean age of participants was 14.7 years (43.4% female), mean duration of diabetes was 1.3 years, and mean HbA1c level was 8.0% (63.4 mmol/mol). After adjustment for age, sex, duration of diabetes, blood pressure, blood lipid levels, body mass index, and smoking, the odds ratio for mean HbA1c <6.5% (<48 mmol/mol) compared with 6.5-6.9% (48-52 mmol/mol) for any retinopathy (simplex or worse) was 0.77 (95% confidence interval 0.56 to 1.05, P=0.10), for preproliferative diabetic retinopathy or worse was 3.29 (0.99 to 10.96, P=0.05), for proliferative diabetic retinopathy was 2.48 (0.71 to 8.62, P=0.15), for microalbuminuria or worse was 0.98 (0.60 to 1.61, P=0.95), and for macroalbuminuria was 2.47 (0.69 to 8.87, P=0.17). Compared with HbA1c levels 6.5-6.9%, HbA1c levels 7.0-7.4% (53-57 mmol/mol) were associated with an increased risk of any retinopathy (1.31, 1.05 to 1.64, P=0.02) and microalbuminuria (1.55, 1.03 to 2.32, P=0.03). The risk for proliferative retinopathy (5.98, 2.10 to 17.06, P<0.001) and macroalbuminuria (3.43, 1.14 to 10.26, P=0.03) increased at HbA1c levels >8.6% (>70 mmol/mol). The risk for severe hypoglycaemia was increased at mean HbA1c <6.5% compared with 6.5-6.9% (relative risk 1.34, 95% confidence interval 1.09 to 1.64, P=0.005).ConclusionsRisk of retinopathy and nephropathy did not differ at HbA1c levels <6.5% but increased for severe hypoglycaemia compared with HbA1c levels 6.5-6.9%. The risk for severe complications mainly occurred at HbA1c levels >8.6%, but for milder complications was increased at HbA1c levels >7.0%.
OBJECTIVE
Type 2 diabetes all-cause mortality (ACM) and myocardial infarction (MI) glycemic legacy effects have not been explained. We examined their relationships with prior individual HbA1c values ...and explored the potential impact of instituting earlier, compared with delayed, glucose-lowering therapy.
RESEARCH DESIGN AND METHODS
Twenty-year ACM and MI hazard functions were estimated from diagnosis of type 2 diabetes in 3,802 UK Prospective Diabetes Study participants. Impact of HbA1c values over time was analyzed by weighting them according to their influence on downstream ACM and MI risks.
RESULTS
Hazard ratios for a one percentage unit higher HbA1c for ACM were 1.08 (95% CI 1.07–1.09), 1.18 (1.15–1.21), and 1.36 (1.30–1.42) at 5, 10, and 20 years, respectively, and for MI was 1.13 (1.11–1.15) at 5 years, increasing to 1.31 (1.25–1.36) at 20 years. Imposing a one percentage unit lower HbA1c from diagnosis generated an 18.8% (95% CI 21.1–16.0) ACM risk reduction 10–15 years later, whereas delaying this reduction until 10 years after diagnosis showed a sevenfold lower 2.7% (3.1–2.3) risk reduction. Corresponding MI risk reductions were 19.7% (22.4–16.5) when lowering HbA1c at diagnosis, and threefold lower 6.5% (7.4–5.3%) when imposed 10 years later.
CONCLUSIONS
The glycemic legacy effects seen in type 2 diabetes are explained largely by historical HbA1c values having a greater impact than recent values on clinical outcomes. Early detection of diabetes and intensive glucose control from the time of diagnosis is essential to maximize reduction of the long-term risk of glycemic complications.
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