How valid is a prescription-based multimorbidity index (Rx-risk) in predicting mortality in the Outcomes and Multimorbidity In Type 2 diabetes (OMIT) study? A nation-wide registry-based cohort study from Norway.

OBJECTIVE: The prescription-based Rx-risk index has previously been developed to measure multimorbidity. We aimed to adapt and evaluate the validity of the Rx-risk index in prediction of mortality among persons with type 2 diabetes. DESIGN: Registry-based study. SETTING: Adults with type 2 diabetes in Norway identified within the 'Outcomes and Multimorbidity In Type 2 diabetes' cohort, with linkage to prescriptions from the Norwegian Prescription Database and mortality from the Population Registry. PARTICIPANTS: We defined a calibration sample of 42 290 adults diagnosed with type 2 diabetes 1950-2013, and a temporal validation sample of 7085 adults diagnosed 2014-2016 to evaluate the index validity over time PRIMARY OUTCOME MEASURE: All-cause mortality METHODS: For the calibration sample, dispensed drug prescriptions in 2013 were used to define 44 morbidity categories. Weights were estimated using regression coefficients from a Cox regression model with 5 year mortality as the outcome and all morbidity categories, age and sex included as covariates. The Rx-risk index was computed as a weighted sum of morbidities. The validity of the index was evaluated using C-statistic and calibration plots. RESULTS: In the calibration sample, mean (SD) age at start of follow-up and duration of diabetes was 63.8 (12.4) and 10.1 (7.0) years, respectively. The overall C-statistic was 0.82 and varied from 0.74 to 0.85 when stratifying on age groups, sex, level of education and country of origin. In the validation sample, mean (SD) age and duration of diabetes was 59.7 (13.0) and 2.0 (0.8) years, respectively. Despite younger age, shorter duration of diabetes and later time period, the C-index was high both in the total sample (0.84) and separately for men (0.83) and women (0.84). CONCLUSIONS: The Rx-risk index showed good discrimination and calibration in predicting mortality and thus presents a valid tool to assess multimorbidity among persons with type 2 diabetes.

High prevalence of retinopathy in young-onset type 2 diabetes and possible sex differences: insights from Norwegian general practice.

INTRODUCTION: People with young-onset type 2 diabetes (YOD), defined as diabetes diagnosis before age 40, have a high lifetime risk of vascular complications. We aimed to estimate the prevalence of YOD among adults with type 2 diabetes (T2D) in Norwegian general practice and explore associations between age at diabetes diagnosis and retinopathy overall and in men and women. RESEARCH DESIGN AND METHODS: We collected cross-sectional data from general practice electronic medical records of 10 241 adults with T2D in 2014, and repeated measurements of hemoglobin A1c (HbA1c) from 2012 to 2014. Using multivariate logistic regression, we assessed associations between YOD and later-onset T2D, sex and retinopathy. RESULTS: Of all individuals with T2D, 10% were diagnosed before 40 years of age in both sexes. Compared with later-onset T2D, HbA1c increased faster in YOD, and at the time of diagnosis HbA1c was higher in men, particularly in YOD. Retinopathy was found in 25% with YOD, twice as frequently as in later onset. After adjustments for confounders (age, country of origin, education, body mass index), OR of retinopathy was increased in both men with YOD (OR 2.6 (95% CI 2.0 to 3.5)) and women with YOD (OR 2.2 (1.5 to 3.0)). After further adjustments for potential mediators (diabetes duration and HbA1c), the higher OR persisted in men with YOD (OR 1.8 (1.3 to 2.4)) but was attenuated and no longer significant for women with YOD. CONCLUSIONS: Retinopathy prevalence was more than twice as high in YOD as in later-onset T2D. The increased likelihood of retinopathy in YOD was partly mediated by higher HbA1c and longer T2D duration, but after accounting for these factors it remained higher in men with YOD.

Insulin initiation in patients with type 2 diabetes is often delayed, but access to a diabetes nurse may help-insights from Norwegian general practice.

Objective: We opted to study how support staff operational capacity and diabetes competences may impact the timeliness of basal insulin-initiation in general practice patients with type 2 diabetes (T2D).Design/Setting/Outcomes: This was an observational and retrospective study on Norwegian primary care patients with T2D included from the ROSA4-dataset. Exposures were (1) support staff size, (2) staff size relative to number of GPs, (3) clinic access to a diabetes nurse and (4) share of staff with diabetes course (1 and 2 both relate to staff operational capacity, whereas 3 and 4 are both indicatory of staff diabetes competences). Outcomes were 'timely basal insulin-initiation' (primary) and 'attainment of HbA1c<7%' after insulin start-up (secondary). Associations were analyzed using multiple linear regression, and directed acyclic graphs guided statistical adjustments.Subjects: Insulin naïve patients with 'timely' (N = 294), 'postponed' (N = 219) or 'no need of' (N = 3,781) basal insulin-initiation, respectively.Results: HbA1c [median (IQR)] increased to 8.8% (IQR, 8.0, 10.2) prior to basal insulin-initiation, which reduced HbA1c to 7.3 (6.8-8.1) % by which only 35% of the subjects reached HbA1c <7%. Adjusted risk of 'timely basal insulin-initiation' was more than twofold higher if access to a diabetes nurse (OR = 2.40, [95%CI, 1.68, 3.43]), but related only vaguely to staff size (OR = 1.01, [95%CI, 1.00, 1.03]). No other staff factors related significantly to neither the primary nor the secondary outcome.Conclusion: In Norwegian general practice, insulin initiation in people with T2D may be affected by therapeutic inertia but access to a diabetes nurse may help facilitating more timely insulin start-up.

In patients with type 2 diabetes (T2D) cared for by their general practice physician (GP), insulin therapy was susceptible to therapeutic inertia.In Norwegian general practice, chance of timely basal insulin-initiation was found more than two-fold higher if the GP had access to a diabetes nurse.In contrast, the timeliness of basal insulin-initiation in general practice patients with T2D seemed unaffected by share of support staff with diabetes course and by factors indicatory of support staff overall operational capacity.In Norwegian general practice, a diabetes nurse seems to offer unique clinical benefits to the care of insulin treated patients with T2D.

Level of education is associated with coronary heart disease and chronic kidney disease in individuals with type 2 diabetes: a population-based study.

INTRODUCTION: To study the relationship between education level and vascular complications in individuals with type 2 diabetes in Norway. RESEARCH DESIGN AND METHODS: Multiregional population-based cross-sectional study of individuals with type 2 diabetes in primary care. Data were extracted from electronic medical records in the period 2012-2014. Information on education level was obtained from Statistics Norway. Using multivariable multilevel regression analyses on imputed data we analyzed the association between education level and vascular complications. We adjusted for age, sex, HbA1c, low-density lipoprotein cholesterol, systolic blood pressure, smoking and diabetes duration. Results are presented as ORs and 95% CIs. RESULTS: Of 8192 individuals with type 2 diabetes included, 34.0% had completed compulsory education, 49.0% upper secondary education and 16.9% higher education. The prevalence of vascular complications in the three education groups was: coronary heart disease 25.9%, 23.0% and 16.9%; stroke 9.6%, 7.4% and 6.6%; chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2) 23.9%, 16.8% and 12.6%; and retinopathy 13.9%, 11.5% and 11.7%, respectively. Higher education was associated with lower odds for coronary heart disease (OR 0.59; 95% CI 0.49 to 0.71) and chronic kidney disease (OR 0.75; 95% CI 0.60 to 0.93) compared with compulsory education when adjusting for age, sex, HbA1c, low-density lipoprotein cholesterol, systolic blood pressure, smoking and diabetes duration. CONCLUSIONS: In a country with equal access to healthcare, high education level was associated with lower odds for coronary heart disease and chronic kidney disease in individuals with type 2 diabetes.

Cohort profile: Outcomes & Multi-morbidity In Type 2 diabetes (OMIT) - a national registry-based observational cohort with focus on care and treatment of key high-risk groups in Norway.

PURPOSE: The 'Outcomes & Multi-morbidity in Type 2 Diabetes' (OMIT) is an observational registry-based cohort of Norwegian patients with type 2 diabetes (T2D) established to study high-risk groups often omitted from randomised clinical trials. PARTICIPANTS: The OMIT cohort includes 57 572 patients with T2D identified via linkage of Norwegian Diabetes Register for Adults and the Rogaland-Oslo-Salten-Akershus-Hordaland study, both offering data on clinical patient characteristics and drug prescriptions. Subsequently these data are further linked to the Norwegian Prescription Database for dispensed medications, the Norwegian Population Register for data on death and migration, Statistics Norway for data on socioeconomic factors and ethnicity and the Norwegian Directorate of Health for data on the general practices and clinical procedures involved in the care of cohort patients. OMIT offers large samples for key high-risk patient groups: (1) young-onset diabetes (T2D at age <40 years) (n=6510), (2) elderly (age >75 years) (n=15 540), (3) non-Western ethnic minorities (n=9000) and (4) low socioeconomic status (n=20 500). FINDINGS TO DATE: On average, patient age and diabetes duration is 67.4±13.2 and 12.3±8.3 years, respectively, and mean HbA1c for the whole cohort through the study period is 7.6%±1.5% (59.4±16.3 mmol/mol), mean body mass index (BMI) and blood pressure is 30.2±5.9 kg/m2 and 135±16.1/78±9.8 mm Hg, respectively. Prevalence of retinopathy, coronary heart disease and stroke is 10.1%, 21% and 6.7%, respectively. FUTURE PLANS: The OMIT cohort features 5784 subjects with T2D in 2006, a number that has grown to 57 527 in 2019 and is expected to grow further via repeated linkages performed every third to fifth year. At the next wave of data collection, additional linkages to Norwegian Patient Registry and Norwegian Cause of Death Registry for data on registered diagnoses and causes of death, respectively, will be performed.

Escitalopram Ameliorates Hypercortisolemia and Insulin Resistance in Low Birth Weight Men With Limbic Brain Alterations.

Context: Low birth weight (LBW; <2500 g) is linked to the development of insulin resistance and limbic-hypothalamic-pituitary-adrenal (LHPA) axis hyperactivity. Objective: Our first aim was to study insulin action, LHPA axis function, and limbic brain structures in young, healthy LBW men vs normal birthweight (NBW) controls (part 1). Our second aim was to investigate the effects of escitalopram vs placebo in LBW men in the LHPA axis and insulin sensitivity (part 2). Design Setting, Participants, and Intervention: The maximal (Rdmax) and submaximal (Rdsubmax) rates of insulin-stimulated glucose turnover, LHPA axis, and brain morphology were examined in 40 LBW men and 20 matched NBW men using two-stage hyperinsulinemic euglycemic clamp, 24-hour hormone plasma profiles, and magnetic resonance imaging. Subsequently, all LBW subjects underwent randomized and double-blind treatment with escitalopram 20 mg/d or placebo for 3 months followed by a complete reexamination. Main Outcome Measures (Part 2): Changes in Rdmax/Rdsubmax and plasma-free cortisol 24-hour area under the curve. Results: In LBW vs NBW, Rdsubmax and Rdmax were ∼16% (P = 0.01) and ∼12% (P = 0.01) lower, respectively, and 24-hour free cortisol levels were ∼20% higher (P = 0.02), primarily driven by a ∼99% increase at 05:00 am (P < 0.001). Furthermore, these changes were related to structural alterations within left thalamus and ventromedial prefrontal cortex. However, in LBW men, exposure to escitalopram normalized the free cortisol levels and improved the Rdsubmax by ∼24% (P = 0.04) compared with placebo. Conclusions: LBW vs NBW displayed alterations in key brain structures modulating the LHPA axis, elevated free cortisol levels, and insulin resistance. Escitalopram administration ameliorated these defects, suggesting a potential for LHPA axis modulation compounds to improve insulin action in LBW subjects.

Impaired insulin action despite upregulation of proximal insulin signaling: novel insights into skeletal muscle insulin resistance in liver cirrhosis.

BACKGROUND/AIMS: Disturbance in glucose metabolism is a common feature in liver diseases and this is associated with skeletal muscle insulin resistance. However, the underlying molecular mechanisms are unclear. To characterize skeletal muscle insulin resistance associated with liver disease, we examined muscles from animals after an acute, 5 weeks perturbation of the common bile duct. Clinical findings, elevated plasma levels of liver enzymes and histological examinations confirmed cirrhosis. METHODS/RESULTS: : Cirrhotic animals were insulin resistant and this was associated with reduced glucose transport into muscles. Interestingly, activity in the proximal part of the insulin signaling cascade was not decreased, as evinced by increased activity of key enzymes in the signal to glucose transport. Expression of the glucose transporter, GLUT4, was normal. So together these results indicate that signaling downstream of PKB/Akt and/or the translocation of GLUT4 is impaired in skeletal muscle from cirrhotic animals. CONCLUSIONS: In conclusion, in an animal model of liver cirrhosis whole body insulin resistance is associated with insulin resistance in skeletal muscles. Unlike other common forms of insulin resistance, muscles from cirrhotic animals have increased activity in the proximal insulin signaling cascade. This emphasizes the fact that skeletal muscle insulin resistance associated with liver cirrhosis is a unique entity.