Improved control of blood pressure and albuminuria among patients with type-2 diabetes in Finnish open care.

Risk of cardiovascular events within the diabetic population has decreased and survival increased with patients living longer and thus facing the development of end-stage renal disease (ESRD). This calls for good care of patient with diabetes with a focus on hypertension. Patient data were collected from 42 Finnish primary care centres. Each was asked to enrol 10-12 consecutive patients with type-2 diabetes between March 2011 and August 2012. Along with the office blood pressure measurements and laboratory tests, the presence of albuminuria was measured and glomerular filtration rate estimated (eGFR). The 2013 ESH criteria for diabetic hypertensive patients (<140/85 mmHg) was reached by 39% of all 625 study patients and 38% of the pharmacologically treated 520 patients. The absence of detectable albumin in urine was significantly associated with the control of systolic blood pressure and achievement of treatment goals. Beta blockers were the most common antihypertensive agents and patients treated with them had lower eGFR compared to those not treated with these agents. The blood pressure of patients was not in full concordance with the present guideline recommendations. However, satisfactory improvement in blood pressure control, reduction of albuminuria and hence ESRD prevention was achieved.

Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: rationale and design of the epidemiological studies within the IMI DIRECT Consortium.

AIMS/HYPOTHESIS: The DIRECT (Diabetes Research on Patient Stratification) Study is part of a European Union Framework 7 Innovative Medicines Initiative project, a joint undertaking between four industry and 21 academic partners throughout Europe. The Consortium aims to discover and validate biomarkers that: (1) predict the rate of glycaemic deterioration before and after type 2 diabetes onset; (2) predict the response to diabetes therapies; and (3) help stratify type 2 diabetes into clearly definable disease subclasses that can be treated more effectively than without stratification. This paper describes two new prospective cohort studies conducted as part of DIRECT. METHODS: Prediabetic participants (target sample size 2,200-2,700) and patients with newly diagnosed type 2 diabetes (target sample size ~1,000) are undergoing detailed metabolic phenotyping at baseline and 18 months and 36 months later. Abdominal, pancreatic and liver fat is assessed using MRI. Insulin secretion and action are assessed using frequently sampled OGTTs in non-diabetic participants, and frequently sampled mixed-meal tolerance tests in patients with type 2 diabetes. Biosamples include venous blood, faeces, urine and nail clippings, which, among other biochemical analyses, will be characterised at genetic, transcriptomic, metabolomic, proteomic and metagenomic levels. Lifestyle is assessed using high-resolution triaxial accelerometry, 24 h diet record, and food habit questionnaires. CONCLUSIONS/INTERPRETATION: DIRECT will yield an unprecedented array of biomaterials and data. This resource, available through managed access to scientists within and outside the Consortium, will facilitate the development of new treatments and therapeutic strategies for the prevention and management of type 2 diabetes.

Insulin exposure mitigates the increase of arterial stiffness in patients with type 2 diabetes and albuminuria: an exploratory analysis.

AIMS: Insulin possesses both vasodilatory and sympathomimetic activities. The aim was to examine the relationship between changes in insulin exposure and arterial stiffness in type 2 diabetes (T2D). METHODS: Patients with T2D with (n = 22) or without (n = 24) albuminuria, and non-diabetic controls (n = 25) were randomized to a crossover study having a breakfast with or without pre-meal rapid-acting insulin. Pulse wave velocity (PWV) was measured at 30 min before and at 60-min intervals up to 240 min after the breakfast. RESULTS: At baseline, both postprandial aortic (p = 0.022) and brachial (p = 0.011) PWV were higher in individuals with T2D than in healthy controls irrespective of the presence of albuminuria. In patients with albuminuria, weight-adjusted insulin dose correlated inversely with the excursion of the aortic (r = - 0.412, p = 0.006) and brachial (r = - 0.372; p = 0.014) PWV. Similarly, circulating endogenous insulin concentrations correlated inversely with the aortic (r = - 0.347, p = 0.026) and brachial (r = - 0.622, p = <0.001) PWV. No correlations between insulin and PWV were observed in patients without albuminuria or in healthy controls. CONCLUSIONS: The inverse correlation between insulin and PWV in T2D with albuminuria may reflect a vasorelaxing effect of insulin. CLINICAL TRIAL REGISTRATION NUMBER: The study was registered (clinicaltrials.gov) with the identifier of NCT01159938.

Influence of Postprandial Hyperglycemic Conditions on Arterial Stiffness in Patients With Type 2 Diabetes.

CONTEXT: Patients with type 2 diabetes (T2D) are at an increased risk of cardiovascular disease. OBJECTIVE: The objective of the study was to determine whether postprandial hyperglycemia affects arterial function in T2D. DESIGN: A single-center, open-label study of three groups of men were studied: 1) T2D patients with albuminuria (n = 22), 2) T2D patients without albuminuria (n = 24), and 3) nondiabetic controls (n = 25). Patients were randomized to a two-period crossover study schedule, ingesting breakfast, with or without insulin lispro (to induce low or high postprandial glycemia). MAIN OUTCOME MEASURES: Arterial stiffness was assessed by calculating pulse wave velocity (PWV) and augmentation index using applanation tonometry, and endothelial dysfunction was assessed using peripheral arterial tonometry, 30 minutes before breakfast and up to 240 minutes after breakfast. RESULTS: At baseline, arterial stiffness was increased in patients. When adjusted for age and body mass index, in a combined group of patients with and without albuminuria, brachial PWV was higher during low (P = .032) and high (P = .038) postprandial glycemia vs controls. These differences were driven by the albuminuria group vs controls during low (P = .014) and high (P = .018) postprandial glycemia. No differences were observed in aortic PWV, augmentation index, or peripheral arterial tonometry ratio between patients and controls. Endothelin-1 and IL-6 were higher, and superoxide dismutase was lower, during postprandial hyperglycemia in T2D patients vs controls. CONCLUSIONS: In patients with T2D and albuminuria, brachial PWV was higher under postprandial hyperglycemic conditions, relative to controls. These data suggest that hyperglycemia induces an increase in stiffness of intermediate-sized arteries. We found no changes in other parts of the arterial bed.

Cholesterol metabolism in type 1 diabetes.

Little information is available on cholesterol absorption and synthesis in human type 1 diabetes. We studied these variables using serum cholesterol precursor sterol ratios to cholesterol as surrogate markers of cholesterol synthesis and those of cholestanol and plant sterols to reflect cholesterol absorption in seven type 1 diabetic subjects and in five age- and body weight-matched control subjects. Total and lipoprotein cholesterol levels were similar, but triglycerides in intermediate-density lipoprotein (IDL) and LDL were higher in type 1 diabetic than in control subjects. Most of the marker sterols were transported by LDL and HDL in both groups. The percentage of esterified cholesterol was lower in triglyceride-rich lipoproteins in diabetic patients than in control subjects. The ratios of the absorption marker sterols in serum were higher, and those of the synthesis markers were lower in type 1 diabetic than in control subjects. The increased cholestanol ratios were seen in all lipoproteins, and those of free and total plant sterols were mainly in LDL, whereas the decreased free and total synthesis markers were mainly in all lipoproteins. In conclusion, high absorption and low synthesis marker sterols seem to characterize human type 1 diabetes. These findings could be related to low expression of ABC G/5 G/8 genes, resulting in high absorption of cholesterol and sterols in general and low synthesis of cholesterol compared with type 2 diabetes.

Low synthesis and high absorption of cholesterol characterize type 1 diabetes.

OBJECTIVE: Streptozotocin-induced type 1 diabetes in experimental animals inhibits cholesterol synthesis and increases cholesterol absorption. In contrast to human type 2 diabetes, virtually no information is available on cholesterol synthesis and absorption in type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied the variables of cholesterol metabolism in 27 patients with type 1 diabetes and in 10 patients with type 2 diabetes matched for body weight, using cholesterol precursor sterol ratios to cholesterol as surrogate markers of synthesis, and those of cholestanol and plant sterols of cholesterol absorption. Glucose control was good in all subjects. RESULTS: Total and HDL cholesterol and LDL triglycerides were higher in type 2 than in type 1 diabetes. Serum sterols, measured also in VLDL, intermediate-density lipoprotein (IDL), LDL, and HDL, were transported up to >90% by LDL and HDL in type 1 diabetes. The ratios of all absorption sterols in serum and in each lipoprotein were higher, and those of the synthesis markers, especially cholestenol and lathosterol, were lower in type 1 than in type 2 diabetes. CONCLUSIONS: In contrast to type 2 diabetes, the findings in type 1 diabetes could be related to low expression of ABC G/5 G/8 genes, resulting in high absorption of cholesterol and sterols in general and low synthesis of cholesterol.

High prevalence of chronic kidney disease in Finnish patients with type 2 diabetes treated in primary care.

OBJECTIVE: To examine the prevalence of chronic kidney disease (CKD) and related cardiovascular morbidity in a cross-sectional population in patients with type 2 diabetes (T2D) treated in a primary care setting in Finland. RESEARCH DESIGN AND METHODS: Data were collected and recorded from 42 primary care centres, which recruited 629 patients diagnosed with type 2 diabetes (T2D) to this non-interventional study. Data including patient characteristics, kidney function and albuminuria, blood pressure, HbA1c, lipid and lipoprotein levels, and diabetes duration as well as current medication was collected in each patient. RESULTS: In the final study population of 625 patients, the mean age was 67 years (range 29-92 years), BMI 32.8 kg/m(2) (95% CI 32-33), blood pressure 142/80 mmHg (140-143/80-81) and HbA1c 7.1% (7.0-7.2) (53.8 mmol/mol, 53-55) and the median duration of diabetes was 9.2 years ranging from newly diagnosed to 43 years. History of dyslipidemia had in 73.3% of patients, 27.8% had cardiovascular disease and 82.7% had hypertension. The primary endpoint, prevalence of CKD of any grade (1-5) or albuminuria, was 68.6%. Regarding declined renal function, 16.2% of patients had an estimated glomerular filtration rate (eGFR) <60 ml/min/1.72 m(2), classifying as CKD 3-5. Only one patient was within CKD5. Regarding renal damage, albuminuria was present in 24.3% of patients, with microalbuminuria in 17.1% and macroalbuminuria in 7.2%, respectively. Combining the patients with CKD 3-5 and/or the presence of albuminuria, 34.7% seemed to suffer from significant CKD. The proportion of patients with albuminuria increased with a decrease in glomerular filtration rate. Historically, diabetic nephropathy had been diagnosed in 24.3% of the patients. CONCLUSIONS: Nearly 70% of patients with T2D treated in primary care in Finland have some sign of CKD and nearly half of all T2D patients have a significant CKD. However, only half of the latter had it diagnosed and documented in their patient charts, thus highlighting the importance of performing routine screening of nephropathy by measuring both albuminuria and eGFR in patients with T2D. Prevention of this complication with active therapy for risk factors, such as hypertension and dyslipidemia is warranted.

Resource utilisation and clinical data before and after switching between short-acting human insulin and rapid-acting insulin analogues in patients with type 2 diabetes: the SWING study.

AIM: SWING was a prospective, observational study conducted in nine European countries primarily to assess direct treatment costs when switching from short-acting human insulins to rapid-acting insulin analogues (H-A) or vice versa (A-H) in patients with type 2 diabetes. METHODS: Data were collected at a baseline visit (time of switch) and at approximately 3, 6 and 12 months post-switch. RESULTS: In total, 2389 patients switched from H-A (n=2203) or A-H (n=186); another 603 were enrolled but ineligible. Mean (SD) direct diabetes-related costs (pro-rated to account for variable visit schedules) were €548.7 (865.8) 6 months prior to switch, €625.6 (1474.9) at 0-6 months and €568.6 (590.7) 6-12 months following switch for H-A, and €544.5 (421.0), €481.0 (301.5) and €461.6 (335.0) for A-H, respectively. Mean (SD) HbA(1c) decreased over 12 months by 1.08 (1.53)% units H-A and 1.17 (1.45)% units A-H. A small decline in hypoglycaemia occurred over time, but there were no clinically meaningful changes in mean PROs. CONCLUSIONS: There were small changes in mean direct diabetes-related costs (following adjustment for time interval) in patients switching in either direction. Improvements in mean HbA(1c) and incidence of hypoglycaemia cannot necessarily be attributed to therapeutic switch.

Managing diabetes during pregnancy with insulin lispro: a safe alternative to human insulin.

OBJECTIVE: To assess the safety of the use of insulin lispro during pregnancy on the basis of published literature and to report on any related efficacy findings. METHODS: The National Center for Biotechnology Information Entrez Database PubMed (http://www.ncbi. nlm.nih.gov/pubmed/) was used to search for citations from MEDLINE in the November 2009 time frame that contained safety data and efficacy results on the use of insulin lispro during pregnancy. RESULTS: From the MEDLINE search, we identified a total of 27 publications (with 1,265 pregnancies) with relevant information, which were included in this report. No statistically significant differences in the rates of occurrence of congenital anomalies or spontaneous abortions associated with the use of insulin lispro during pregnancy, in comparison with the use of human insulin, were reported. Moreover, in comparison with human insulin, insulin lispro was reported to result in improved glycemic control, as demonstrated by lower postprandial glucose concentrations and hemoglobin A1c levels. CONCLUSION: The current review of the published literature indicates that insulin lispro is a safe alternative to human insulin with similar perinatal outcomes and potentially improved glycemic control in the management of diabetes during pregnancy.

Recruitment to a clinical trial improves glycemic control in patients with diabetes.

OBJECTIVE: We assessed the effect upon A1C of recruitment to a clinical trial in patients with diabetes who had been screened and interviewed to determine eligibility but whose therapy was otherwise unchanged. RESEARCH DESIGN AND METHODS: Eligible trials were selected from the global program of an insulin manufacturer. Included were studies in which patients were seen on a single screening visit, pharmaceutical therapy was not altered before randomization, and A1C was measured in a central laboratory at both screening and randomization. Three trials involving patients with type 1 diabetes (n = 429) and three trials involving patients with type 2 diabetes (n = 611) were identified for analysis. The main outcome measure was change in A1C. Separate regression equations on the change in A1C were fitted for type 1 and type 2 diabetes and included effects of baseline A1C and the interval between the screening and randomization visits. RESULTS: A1C changed by -0.13% (range +0.09 to -0.26%) in those with type 1 diabetes at a median of 28 days and by -0.16% (-0.14 to -0.27%) for those with type 2 diabetes at a median of 14 days. The mean change in A1C in those with an interval of >or=28 days was -0.24% for those with type 1 diabetes and -0.23% for those with type 2 diabetes. The reduction was proportional to initial A1C, with large decreases in those with the poorest initial control but no overall change in those at or below the 10th percentile of A1C. CONCLUSIONS: Recruitment to a clinical trial, independent of any therapeutic intervention, produces improvements in glucose control.