Patients with multimorbidity have complex health needs but, due to the current traditional disease-oriented approach, they face a highly fragmented form of care that leads to inefficient, ineffective, and possibly harmful clinical interventions. There is limited evidence on available integrated and multidimensional care pathways for multimorbid patients. An expert consensus meeting was held to develop a framework for care of multimorbid patients that can be applied across Europe, within a project funded by the European Union; the Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS). The experts included a diverse group representing care providers and patients, and included general practitioners, family medicine physicians, neurologists, geriatricians, internists, cardiologists, endocrinologists, diabetologists, epidemiologists, psychologists, and representatives from patient organizations. Sixteen components across five domains were identified (Delivery of Care; Decision Support; Self Management Support; Information Systems and Technology; and Social and Community Resources). The description and aim of each component are described in these guidelines, along with a summary of key characteristics and relevance to multimorbid patients. Due to the lack of evidence-based recommendations specific to multimorbid patients, this care model needs to be assessed and validated in different European settings to examine specifically how multimorbid patients will benefit from this care model, and whether certain components have more importance than others.

OBJECTIVETo describe the prevalence and determinants of hyperfiltration (glomerular filtration rate [GFR] ≥120 mL/min/1.73 m2), GFR decline, and nephropathy onset or progression in type 2 diabetic patients with normo- or microalbuminuria.RESEARCH DESIGN AND METHODSWe longitudinally studied 600 hypertensive type 2 diabetic patients with albuminuria <200 μg/min and who were retrieved from two randomized trials testing the renal effect of trandolapril and delapril. Target blood pressure (BP) was <120/80 mmHg, and HbA1c was <7%. GFR, albuminuria, and glucose disposal rate (GDR) were centrally measured by iohexol plasma clearance, nephelometry in three consecutive overnight urine collections, and hyperinsulinemic euglycemic clamp, respectively.RESULTSOver a median (range) follow-up of 4.0 (1.7–8.1) years, GFR declined by 3.37 (5.71–1.31) mL/min/1.73 m2 per year. GFR change was bimodal over time: a larger reduction at 6 months significantly predicted slower subsequent decline (coefficient: −0.0054; SE: 0.0009), particularly among hyperfiltering patients. A total of 90 subjects (15%) were hyperfiltering at inclusion, and 11 of 47 (23.4%) patients with persistent hyperfiltration progressed to micro- or macroalbuminuria versus 53 (10.6%) of the 502 who had their hyperfiltration ameliorated at 6 months or were nonhyperfiltering since inclusion (hazard ratio 2.16 [95% CI 1.13–4.14]). Amelioration of hyperfiltration was independent of baseline characteristics or ACE inhibition. It was significantly associated with improved BP and metabolic control, amelioration of GDR, and slower long-term GFR decline on follow-up.CONCLUSIONSDespite intensified treatment, patients with type 2 diabetes have a fast GFR decline. Hyperfiltration affects a subgroup of patients and may contribute to renal function loss and nephropathy onset or progression. Whether amelioration of hyperfiltration is renoprotective is worth investigating.

There are no adequate studies that have formally tested the performance of different estimating formulas in patients with type 2 diabetes both with and without overt nephropathy. Here we evaluated the agreement between baseline GFRs, GFR changes at month 6, and long-term GFR decline measured by iohexol plasma clearance or estimated by 15 creatinine-based formulas in 600 type 2 diabetics followed for a median of 4.0 years. Ninety patients were hyperfiltering. The number of those identified by estimation formulas ranged from 0 to 24:58 were not identified by any formula. Baseline GFR was significantly underestimated and a 6-month GFR reduction was missed in hyperfiltering patients. Long-term GFR decline was also underestimated by all formulas in the whole study group and in hyper-, normo-, and hypofiltering patients considered separately. Five formulas generated positive slopes in hyperfiltering patients. Baseline concordance correlation coefficients and total deviation indexes ranged from 32.1% to 92.6% and from 0.21 to 0.53, respectively. Concordance correlation coefficients between estimated and measured long-term GFR decline ranged from -0.21 to 0.35. The agreement between estimated and measured values was also poor within each subgroup considered separately. Thus, our study questions the use of any estimation formula to identify hyperfiltering patients and monitor renal disease progression and response to treatment in type 2 diabetics without overt nephropathy.

Aims To select a core list of standard outcomes for diabetes to be routinely applied internationally, including patientreported outcomes. Methods We conducted a structured systematic review of outcome measures, focusing on adults with either type 1 or type 2 diabetes. This process was followed by a consensus-driven modified Delphi panel, including a multidisciplinary group of academics, health professionals and people with diabetes. External feedback to validate the set of outcome measures was sought from people with diabetes and health professionals. Results The panel identified an essential set of clinical outcomes related to diabetes control, acute events, chronic complications, health service utilisation, and survival that can be measured using routine administrative data and/or clinical records. Three instruments were recommended for annual measurement of patient-reported outcome measures: the WHO Well-Being Index for psychological well-being; the depression module of the Patient Health Questionnaire for depression; and the Problem Areas in Diabetes scale for diabetes distress. A range of factors related to demographic, diagnostic profile, lifestyle, social support and treatment of diabetes were also identified for case-mix adjustment. Conclusions We recommend the standard set identified in this study for use in routine practice to monitor, benchmark and improve diabetes care. The inclusion of patient-reported outcomes enables people living with diabetes to report directly on their condition in a structured way.

The adiponectin-leptin ratio is associated with insulin resistance, measured with the euglycemic hyperinsulinemic clamp, in Caucasians with T2D. The association with clamp derived sensitivity index is even stronger than that of HOMA, QUICKI, fasting glucose/insulin ratio or McAuley index and is independent of body mass index or glycemic control. The adiponectin-leptin ratio promises to become a new laboratory marker of insulin resistance in T2D.

As exocrine and endocrine pancreatic insufficiency can develop after AP, routine follow-up of patients is necessary, for which serum nutritional panel measurements can be useful.

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Abstract-To assess whether angiotensin-converting enzyme inhibitors and third-generation dihydropyridine calcium channel blockers ameliorate diabetic complications, we compared glomerular filtration rate (GFR; primary outcome), cardiovascular events, retinopathy, and neuropathy in 380 hypertensive type 2 diabetics with albuminuria Ͻ200 mg/min included in a multicenter, double-blind, placebo-controlled trial (DEMAND [Delapril and Manidipine for Nephroprotection in Diabetes]) and randomized to 3-year treatment with manidipine/delapril combination (10/30 mg/d; nϭ126), delapril (30 mg/d; nϭ127), or placebo (nϭ127). GFR was centrally measured by iohexol plasma clearance. Median monthly GFR decline (interquartile range ) on placebo (Pϭ0.87 and Pϭ0.53 versus combined therapy or delapril, respectively). Similar findings were observed when baseline GFR values were not considered for slope analyses. Albuminuria was stable in the 3 treatment groups. The hazard ratio (95% CI) for major cardiovascular events between combined therapy and placebo was 0.17 Pϭ0.023). Among 192 subjects without retinopathy at inclusion, the hazard ratio for developing retinopathy between combined therapy and placebo was 0.27 (0. Pϭ0.048). Among 200 subjects with centralized neurological evaluation, the odds ratios for peripheral neuropathy at 3 years between combined therapy or delapril and placebo were 0.45 (0.24 -0.87; Pϭ0.017) and 0.52 (0.27-0.99; Pϭ0.048), respectively. Glucose disposal rate decreased from 5.8Ϯ2.4 to 5.3Ϯ1.9 mg/kg per min on placebo (Pϭ0.03) but did not change on combined or delapril therapy. Treatment was well tolerated. In hypertensive type 2 diabetic patients, combined manidipine and delapril therapy failed to slow GFR decline but safely ameliorated cardiovascular disease, retinopathy, and neuropathy and stabilized insulin sensitivity. (Hypertension. 2011;58:776-783.) • Online Data Supplement Key Words: ACE inhibitors Ⅲ calcium channel blockers Ⅲ manidipine Ⅲ diabetic nephropathy Ⅲ cardiovascular complications Ⅲ diabetic neuropathy Ⅲ diabetic retinopathy Received April 11, 2011; first decision April 26, 2011; revision accepted August 25, 2011. From the Mario Negri Institute for Pharmacological Research (P.R., I.P.I., A.F., A.P.I., S.R., C.C., N.R., G.N., N.M., B.E.-I., F.G., A.P., G.R.), Clinical Research Center for Rare Diseases "Aldo e Cele Daccò," Ranica, Bergamo, Italy; Unit of Nephrology (P.R., S.R., G.R.), Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy; Neuromuscular Diseases Unit (G.L., A.S., R.L., P.P.), Istituto Di Ricovero e Cura a Carattere Scientifico Foundation "Carlo Besta" Neurological Institute, Milan, Italy; Department for Endocrinology, Diabetes and Metabolic Diseases (P.B., J.Z.), University Medical Centre, Ljubljana, Slovenia; Department of Neuroscience and Biomedical Technologies (G.C. A ngiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists are the antihypertensive agents that more effectively reduce macrovascular disease 1 and limit the onset and progression o...