Chronic Complications Of Type Research Articles

Desaturase activities and metabolic control in type 2 diabetes

The aim of this study was to elucidate the effects of a poor glycemic control on fatty acid composition and desaturase activities in type 2 diabetic patients. Plasma phospholipid fatty acid composition and desaturase activities (estimated from fatty acid product to precursor ratios) were measured in 30 type 2 diabetic patients during poor metabolic control and after achieving a good metabolic control. Significant changes were recorded in the percentages of palmitic, stearic, dihomo- γ-linolenic, docosatetraenoic and docosapentaenoic acid. The delta-5 desaturase activity was significantly higher with poor than with good metabolic control. The changes identified in plasma phospholipid fatty acid composition and the desaturase activity in type 2 diabetic patients go in the opposite direction to those described in similar conditions in type 1 diabetic patients and may be relevant to a better understanding of the role of metabolic control in the progression of chronic complications in type 2 diabetic patients.

Lipid‐lowering therapy in patients with type 2 diabetes: the case for early intervention

Chronic complications of type 2 diabetes, in particular, macrovascular complications, confer substantial morbidity and mortality and adversely affect a patient's quality of life. Early intensive intervention to control cardiovascular risk factors is essential in clinical management. Atherogenic dyslipidaemia characterized by elevated triglycerides, a low level of high-density lipoprotein cholesterol (HDL-C), and an increase in the preponderance of small, dense low-density lipoprotein (LDL) particles, is a key modifiable risk factor for macrovascular diabetic complications. Lowering low-density lipoprotein cholesterol (LDL-C) with a statin (or the combination of statin and ezetimibe) is the main focus for reducing cardiovascular risk in patients with diabetes. However, statins fail to address the residual cardiovascular risk associated with low HDL-C. Fibrates are effective against all components of the atherogenic dyslipidaemia associated with type 2 diabetes. Secondary analyses of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study suggest a role for early treatment with fenofibrate in improving cardiovascular risk reduction in type 2 diabetes and provide safety data supporting the use of fenofibrate in combination with a statin. Data from the FIELD study suggest that fenofibrate may also have potential to impact on microvascular diabetic complications associated with type 2 diabetes. Data are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to evaluate the outcome benefits of combining fenofibrate with a statin in patients with type 2 diabetes. Finally, in view of divergent study results and outstanding data, assessment of the risk of the individual with type 2 diabetes is mandatory to assist clinical decision-making when initiating lipid therapy.

Prasterone [dehydroepiandrosterone] may slow the development of chronic complications in type 2 diabetes mellitus

Prasterone [dehydroepiandrosterone] may slow the development of chronic complications in type 2 diabetes mellitus

Monitorização ambulatorial da pressão arterial e diabete melito tipo 2

Hypertension is one of the main risk factors for the onset and progression of chronic complications in type 2 diabetes mellitus (DM). Ambulatory blood pressure (BP) monitoring (ABPM) provides a better correlation with target organ lesions than BP obtained in the office. Furthermore, it allows the evaluation of distinct BP parameters such as the 24-h, daytime and nighttime systolic and diastolic BP means, BP loads and the absence of nocturnal drop of BP, as well as the identification of white-coat and masked hypertension. DM patients have higher daytime and nighttime BP means than non-DM patients. In addition, one third of normotensive type 2 DM patients have masked hypertension, which is associated with an increase in albuminuria and in left ventricle wall thickness. On the other hand, the prevalence and effect of white-coat hypertension in type 2 DM patients have not yet been properly evaluated. The absence of nocturnal drop of BP does not add information to the 24 h, daytime or nighttime BP measurements, but the nighttime BP means seem to be relevant in DM retinopathy. In conclusion, BP determination by ABPM allows better patient risk stratification for the development of DM chronic complications and is an essential instrument for effective BP control in these patients.

Dehydroepiandrosterone Administration Counteracts Oxidative Imbalance and Advanced Glycation End Product Formation in Type 2 Diabetic Patients

Dehydroepiandrosterone (DHEA) has been shown to prevent oxidative stress in several in vivo and in vitro models. This study aimed to evaluate the effects of DHEA administration on oxidative stress, pentosidine concentration, and tumor necrosis factor (TNF)-alpha/TNF-alpha receptor system activity in patients with type 2 diabetes. Twenty patients were enrolled in the study and randomly assigned to the DHEA (n = 10) or placebo (n = 10) group. Twenty healthy sex- and age-matched subjects with normal glucose levels served as control subjects. DHEA was given as a single daily dose of 50 mg for 12 weeks. Oxidative stress parameters were significantly higher in diabetic patients versus control subjects. Pentosidine levels, as well as soluble TNF receptor (sTNF-R)I and sTNF-RII, were also higher in diabetic patients. After DHEA, plasma levels of reactive oxygen species and hydroxynonenal dropped by 53 and 47%, respectively, whereas the nonenzymatic antioxidants glutathione and vitamin E increased (+38 and +76%, respectively). The same changes in oxidative parameters were detected in peripheral blood mononuclear cells (PBMCs). DHEA treatment also induced a marked decrease of pentosidine plasma concentration in diabetic patients (-50%). Moreover, the TNF-alpha/TNF-alpha receptor system was shown to be less activated after DHEA treatment, in both plasma and PBMCs. Data indicate that DHEA treatment ameliorates the oxidative imbalance induced by hyperglycemia, downregulates the TNF-alpha/TNF-alpha receptor system, and prevents advanced glycation end product formation, suggesting a beneficial effect on the onset and/or progression of chronic complications in type 2 diabetic patients.

Preventing microalbuminuria in patients with type 2 diabetes

The public health burden of type 2 diabetes mellitus has been dramatically increasing world-wide. The chronic complications of type 2 diabetes play an important role in decreasing life expectancy and adversely affecting quality of life. Diabetic nephropathy, which is originally microvascular in nature, is widely considered an important complication of diabetes. In prospective clinical investigations, increased urinary albumin excretion proved to be associated not only with subsequent renal outcomes but also with cardiovascular morbidity/mortality independently of other risk factors. Therefore, microalbuminuria as an early sign of increased urinary albumin excretion should be considered important for both treatment and even for prevention. Preventing microalbuminuria might diminish progression to overt nephropathy and, hopefully, might limit cardiovascular events. Regarding primary prevention of diabetic nephropathy, therapeutic intervention should optimally be initiated at the stage of normoalbuminuria. Although additional factors such as smoking cessation, reduction of protein intake, and treatment of lipid abnormalities are important, providing optimal diabetic control as well as targeting optimal blood pressure are the key elements of a prevention strategy in diabetic patients. Recently, the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) documented that a significant decrease of the development of persistent microalbuminuria could be achieved by using an ACE-inhibitor, trandolapril alone or in combination with verapamil SR, a non-dihydropyridine calcium-channel blocker in hypertensive type 2 diabetic patients with normoalbuminuria. The results of this primary-prevention strategy should be corroborated by further investigations to determine whether these beneficial changes could later result in improvement of renal clinical outcomes, macrovascular complications, or both.

Diabetes mellitus exacerbates advanced glycation end product accumulation in the veins of end-stage renal failure patients

The excess accumulation of advanced glycation end products (AGEs) contributes to the chronic complications of type 2 diabetes mellitus (DM) and renal failure. Biopsy specimens (n = 184) of arterial (n = 92) and venous (n = 92) tissues were obtained (radial artery and cephalic vein) from end-stage renal disease (ESRD) patients with or without DM and normal healthy subjects (n = 12) requiring surgery (trauma patients). Immunohistochemical assessment of the blood vessels revealed the presence of pentosidine (AGE marker) in both veins and arteries in 72% of the ESRD patients. The percentage of arteries and veins that showed positive pentosidine staining in ESRD patients with type 2 DM alone was 100% and 92% respectively, in the non-diabetic ESRD patients it was < 70% (for arteries and veins), and in the ESRD patients with hypertension as an additional co-morbidity to type 2 DM it was 70% and 82%, respectively. The veins of ESRD patients with DM showed a strong (+++) positive staining and very strong (++++) positive staining was observed in the patients with DM and hypertension. Only mild (+) or moderate (++) pentosidine staining intensity was observed in the arteries of ESRD patients without or with comorbidities, respectively. The accumulation of AGE in the vein rather than the artery may be a better reflection of the extent of complications of ESRD.

Perception and integration of people living with type 1 diabetes – an empirical study

AbstractBackground: The chronic complications of type 1 diabetes impose a heavy physical, psychological and social burden on people living with the condition. Improved metabolic control reduces the risk of developing chronic complications and could lead to improved well-being for people with diabetes.Aims: The aim of this study was to explore the perceptions of adults with type 1 diabetes who have improved their metabolic control with respect to acceptance, knowledge, social support and their relationships with healthcare providers.Methods: The study included ten people with type 1 diabetes who had achieved and maintained a reduction of 1.5% in their HbA1C during a one-year period. A phenomenological qualitative semi-structured interview was used in the collection of information from the participants. The interviews were analysed using the method of meaning condensation; these were interpreted from a perspective of integration.Results: The study shows differences among people living with diabetes regardin...

Comparisons of the outcomes on control, type of management and complications status in early onset and late onset type 2 diabetes in Asia

Objective To describe the clinical characteristics and chronic diabetic complications in early (EOD) and late onset type 2 diabetes mellitus (LOD) in Asia. Research design and methods Retrospective collection of information (basic patient data, treatment received for diabetes, hypertension, dyslipidaemia, clinical measurements, complications, life-style management, etc.) on paper form and prospective collection of blood samples for HbA 1c assessment were performed. Means, proportions and associated factors were analyzed using non-parametric and logistic regression. Results The frequency of EOD (<30 years) varies in different Asian countries (0.4–5.3%). Overweight (BMI ≥ 23 kg/m 2) was common in both EOD (60%) and LOD (66%). EOD was characterized by significantly higher levels of HbA 1c (median 8.9% versus 7.9%) and FPG (median 9.8 mmol/L versus 8.3 mmol/L) but hypertension was less common (43% versus 59%). Lipid profiles (cholesterol and triglycerides) were similar between both groups of patients. Cataract was more common in LOD and was associated with onset age and diabetes duration whereas an increase in frequency of advanced eye disease, retinopathy and history of photocoagulation was found in EOD cohort. Conclusions In addition to diabetic control and duration of the disease, the onset age conferred risk to certain subsets of chronic complications in type 2 diabetes population.

Prävention bei Diabetes mellitus Typ 1

Primary prevention of type 1 diabetes is as yet not feasible. In contrast, prevention of acute and chronic complications of type 1 diabetes is highly effective. With a near normal blood glucose control the appearance and progression of microvascular complications (i.e. retinopathy, nephropathy and neuropathy) can be significantly reduced. Intensive insulin therapy is the gold standard for treatment of type 1 diabetes.

Glycemic exposure is associated with reduced pulmonary function in type 2 diabetes: the Fremantle Diabetes Study.

To examine prospectively the relationship between diabetes, glycemic control, and spirometric measures. From a community-based cohort, 495 Europid (i.e., of European descent) patients with type 2 diabetes who had no history of pulmonary disease underwent baseline spirometry between 1993 and 1994. A subset of 125 patients was restudied a mean of 7.0 years later. The main outcome measures included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), vital capacity (VC), and peak expiratory flow (PEF) corrected for body temperature, air pressure, and water saturation and were expressed either in absolute terms or as percentage-predicted value for age, sex, and height. Mean percentage-predicted values of each spirometric measure were decreased >10% in the whole cohort at baseline and absolute measures continued to decline at an annual rate of 68, 71, and 84 ml/year and 17 l/min for FVC, FEV1, VC, and PEF, respectively, in the 125 prospectively studied patients. Declining lung function measures were consistently predicted by poor glycemic control in the form of a higher updated mean HbA1c, follow-up HbA1c, or follow-up fasting plasma glucose. In a Cox proportional hazards model, decreased FEV1 percentage-predicted value was an independent predictor of all-cause mortality. Reduced lung volumes and airflow limitation are likely to be chronic complications of type 2 diabetes, the severity of which relates to glycemic exposure. Airflow limitation is a predictor of death in type 2 diabetes after adjusting for other recognized risk factors.

Aggregation of features of the metabolic syndrome is associated with increased prevalence of chronic complications in Type 2 diabetes.

To investigate the association of features of the metabolic syndrome with the prevalence of chronic complications. A cross-sectional study was conducted with 548 patients with Type 2 diabetes mellitus (DM). Metabolic syndrome was diagnosed in the presence of at least two of the following: hypertension, dyslipidaemia, obesity, and microalbuminuria. Patients with the metabolic syndrome (85%) had a higher prevalence of peripheral vascular disease (PVD) (35% vs. 18%), retinopathy (44% vs. 20%), distal sensory neuropathy (DSN) (44% vs. 24%), micro- and macroalbuminuria (38% vs. 28%) and coronary artery disease (CAD) (53% vs. 36%). The more metabolic syndrome features (none/one, two, three or four), the higher the proportion of diabetes complications: PVD 18%, 31%, 37% and 38%; stroke 1.0%, 4.5%, 5.9% and 11.3%; retinopathy 20%, 38%, 42% and 64%; DSN 24%, 32%, 49% and 57%; micro- and macroalbuminuria 28%, 36% and 41%; and CAD 36%, 44%, 52% and 60% (P < 0.05). The metabolic syndrome and the aggregation of its components were significantly associated with macro- and microvascular complications in Type 2 DM patients.

Frequency of chronic complications of type II diabetes.

To assess the frequency of chronic complications of type II diabetes in subjects attending a tertiary care unit in Karachi, Pakistan. A cross-sectional analytical study. First visit of all type II diabetic subjects attending the outpatient department of Baqai Institute of Diabetology and Endocrinology from September 1996 to December 2001. Computerized clinical records of 2199 type II diabetic subjects were analyzed for this study. The clinical and laboratory variables were statistically evaluated with significance at p. Means of glycosylated hemoglobin HbA1c, fasting and random plasma glucose levels, systolic blood pressure, triglycerides and high density lipoproteins (HDL) were higher than the risk indicator value for both genders (p <0.005). Mean body mass index and total blood cholesterol was higher for females only. Hyperglycemia was present in 88%, high HbA1c in 81%, low HDL in 81%, obesity in 66% and hypertriglyceridemia in 54%, neuropathy in 36%, proteinuria in 28% and hypertension in 50% of the subjects. Frequency of obesity, low HDL and hypertension was higher among females (p < 0.001 in each case). Retinopathy (p<0.05), nephropathy (p<0.005), neuropathy (p<0.005) and foot ulcers (p<0.001) were higher among males. Frequency of obesity was significantly higher among those with shorter duration and in younger group while frequency of other complications was higher among those with longer duration and in the older groups. Higher rates of complications were observed compared to previous studies. Certain variables showed significant association with gender and age as described above.

The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT): design and baseline characteristics

Microalbuminuria is an early marker of diabetic nephropathy and its prevention is considered key for the primary prevention of diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors and nondihydropyridine calcium channel blockers (CCBs) have specific renoprotective properties in diabetes, and preliminary evidence is available that they are more effective in combination than either of the two agents alone in limiting albuminuria either in micro- or macroalbuminuric type 2 diabetic patients. The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT) is a prospective, randomized, double-blind parallel-group study primarily aimed at evaluating the possibility of preventing the progression to microalbuminuria (urinary albumin excretion [UAE] rate 20–200 μg/min, i.e., incipient nephropathy) in 1209 hypertensive, type 2 diabetic patients with a normal UAE rate (<20 μg/min). During phase A of the study, patients are randomized to a 3-year treatment with one of the following: (1) a nondihydropyridine CCB (verapamil SR 240 mg/day); (2) an ACE inhibitor (trandolapril 2 mg/day); (3) the combination of the above study drugs (verapamil SR 180 mg/day plus trandolapril 2 mg/day); or (4) placebo. Phase B of the study evaluates the progression to macroalbuminuria (UAE⩾200 μg/min) in patients who progress to microalbuminuria in phase A or are found with microalbuminuria during the screening phase; these patients are randomized to a 2-year treatment with either trandolapril (2 mg/day) alone or verapamil SR (180 mg/day) plus trandolapril (2 mg/day). BENEDICT final results are expected to be available by the end of 2003 for phase A and 2 years later for phase B. The BENEDICT study, in addition to exploring whether primary prevention of diabetic nephropathy is an achievable goal, will also offer an opportunity to study prospectively risk factors of nephropathy and other chronic complications of type 2 diabetes. Here we provide an overview of the protocol and summarize the main baseline demographic, biochemical, and clinical characteristics of randomized participants.

Beta 3-adrenergic receptor gene polymorphism and type 2 diabetes in a Caucasian population.

The beta 3-adrenergic receptor (beta 3-AR) is suspected to play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. A mutation in the beta 3-AR gene (Trp64Arg) has been associated with the capacity of weight gain and with early onset of noninsulin dependent diabetes mellitus (type 2 diabetes). In this study we investigated the prevalence of the two beta 3-AR alleles in a Caucasian population and studied the association between the beta 3-AR genotype and metabolic disorders (obesity and type 2 diabetes). Genomic DNA extracted from peripheral blood leucocytes of 200 Caucasian subjects (137 subjects with and 63 subjects without type 2 diabetes). The MvaI polymorphism of beta 3-AR, which detects the Trp64Arg mutation, was determined by polymerase chain reaction (PCR). We studied the correlation between the Trp64Arg mutation and the body mass index (b.m.i. kg/m2). There was no significant difference between the patients with type 2 diabetes and control subjects in the frequency of the Arg64 allele (5.5% and 4.8%, respectively). Within the group of type 2 diabetes patients were 14 subjects with the Trp64Arg mutation (b.m.i., mean +/- s.d.: 31 +/- 8.5 kg/m2) and 123 without the mutation (b.m.i. 29 +/- 4.8). There was no association between the beta 3-AR gene polymorphism and sex, obesity, blood pressure, glycohaemoglobin concentration, proteinuria. Our results suggest that the Trp64Arg mutation is not a major determinant of metabolic disorders (type 2 diabetes, obesity) and chronic complications of type 2 diabetes in a Dutch population.

Relationship of residual beta-cell function, metabolic control and chronic complications in type 2 diabetes mellitus.

As the relationships between C-peptide levels and metabolic control and chronic complications are poorly known in type 2 diabetes, due to the slow decline of beta-cell function, we evaluated these associations in a cohort of type 2 diabetic patients. After excluding insulin-treated subjects, 1,533 patients were divided according to their C-peptide fasting levels in quartiles. Patients within the lowest C-peptide quartile showed significantly higher duration of diabetes, prevalence of retinopathy and values of HDL-cholesterol, albumin excretion rate and HbA1c, while BMI, diastolic blood pressure, percentages of hypertension and metabolic syndrome, and values of triglycerides and uric acid were significantly higher in the highest C-peptide quartile. The associations between C-peptide and duration of diabetes, AER, HbA1c, retinopathy and the components of the metabolic syndrome remained significant, after multiple adjustments. In conclusion, these data support the hypothesis that a reduced insulin secretion is associated with a longer duration of diabetes and a greater prevalence of microvascular complications, while higher insulin levels are associated with the components of the metabolic syndrome.