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Aims/hypothesis: It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435)., Methods: We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively., Results: The TC and TC-PA models showed better fit than null models (TC: χ 2  = 242, p = 0.004 and χ 2  = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ 2  = 180, p = 0.041 and χ 2  = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle., Conclusions/interpretation: These analyses partially support the mechanisms proposed in the twin-cycle model and highlight mechanistic pathways through which insulin sensitivity and liver fat mediate the association between physical activity and glycaemic control.

Patients with type 2 diabetes are at high risk of cardiovascular disease. Schramm et al. have published a study in which all residents of Denmark aged 30 years or older on 1 January 1997 (approximately 3.3 million individuals) were followed up for 5 years by individual-level linkage of nationwide registers. The study indicated that patients requiring glucose-lowering therapy (oral treatment, insulin, or combined insulin and oral therapy) exhibited a cardiovascular risk comparable to that of nondiabetic individuals with a prior myocardial infarction, irrespective of sex and type of diabetes. In recent AHA and American Diabetes Association guidelines for the primary prevention of cardiovascular disease, all treatment recommendations for patients with type 2 diabetes also apply to those with type 1 diabetes and to both sexes. Epidemiological evidence reported by Schramm et al. is in line with these recommendations.

Objective: The aim of the present study was to examine both the structure, including modes of drug treatment, ambulatory care, and hospital inpatient care, and the costs of health care for drug-treated diabetic patients in Finland., Research Design and Methods: The modes of drug treatment and ambulatory care were studied with the help of a questionnaire given to all diabetic patients obtaining their medication through pharmacies in Finland during a 7-week period in 1989. The questionnaire sought information on drug treatment, site of health care, and frequency of visits to physicians. Hospital inpatient care was evaluated by linking the patient data from the Hospital Discharge Register and the Central Drug Register. The direct costs of health care were calculated by using relevant average costs., Results: A total of 30,266 questionnaires were returned, representing > 70% of all drug-treated diabetic patients receiving medication in the period studied. Of the diabetic patients, 63% were treated by oral medication only, 31% by insulin only, and 6% by a combination of insulin and oral agents. Of the patients in whom diabetes was diagnosed at > or = 30 years of age, 75% were treated at health centers, whereas > 60% of those in whom diabetes was diagnosed at < 30 years of age were treated at outpatient clinics. The mean annual frequency of visits was 4.0 for patients receiving insulin treatment and 3.3 for patients receiving treatment with oral medications. The diabetic patients used 1.5 million hospital inpatient days per year, which was 13% of the total inpatient days in Finland. Of the inpatient days, 20% were for diabetes as the principal cause, 52% for diabetes-related diseases, and 28% for causes unrelated to diabetes. The direct costs of the health care of drug-treated diabetic patients in 1989 were 5.8% of the total costs of health care in Finland and were three times higher than the average costs of care for nondiabetic individuals. The direct costs were divided into inpatient care (81%), medication (9%), ambulatory care (8%), and self-care equipment (2%)., Conclusions: Hospital inpatient care is the major contributor to the excess of health care expenditures for diabetic patients.