Lipid disorders in type 1 and type 2 diabetes

Atherosclerotic cardiovascular disease is the most important cause of morbidity and mortality in diabetic subjects. Abnormalities in circulating lipids and lipoproteins are considered to be important risk factors for cardiovascular disease because they occur with increased frequency in diabetic individuals. Because reversal of these abnormalities carries the potential for preventing or ameliorating cardiovascular disease, their identification and management with other cardiovascular disease risk factors deserve equal importance to the management of hyperglycemia and frequently are complementary to it.     

Angina pectoris in type A and type B cardiac patients

The type A behavior pattern is characterized by excessive competitive drive, a sense of time urgency, enhanced aggressiveness, hostility and a persistent desire for recognition. Type A behaviour is widely recognized as a risk factor in coronary heart disease. This study investigated whether type As and Bs differ in their experience of pain and pain coping efforts. A group of type A (n = 35) and a group of type B (n = 19) cardiac disease patients served as subjects. All subjects underwent diagnostic treadmill testing and were compared on a variety of pain measures. There were no differences between type As and Bs in age, sex, presence of state or trait anxiety or severity of cardiac disease. Type A patients, however, were much more likely than type Bs to be classified on the New York Heart Association (NYHA) functional angina scale as having more severe pain and functional limitation. Type As were also less likely to use pain coping strategies to deal with their pain. Those who assess pain and functional impairment in cardiac patients using the NYHA scale should be aware that type A personality characteristics may affect their assessments. Type A patients who tend to make little use of pain coping strategies may benefit from systematic training in pain control methods. Additional research is needed to examine whether type A-B differences in pain and pain coping strategies may affect risks of coronary morbidity and mortality.     

Spectrum of proteinuria in type I and type II diabetes

We prospectively investigated the evolution of proteinuria in 52 type I diabetics over 7.8 +/- 0.3 (mean +/- SE) yr and in 61 type II diabetics over 6.4 +/- 0.3 yr. Measurements of renal protein clearance were performed serially, and the time course of proteinuria was classified in each subject based on a threshold albumin clearance of 11 nl/s, equivalent to a urinary albumin excretion rate of 30 micrograms/min. The classification based on this threshold yielded four distinct patterns of albuminuria: minimal, intermittent, progressing, and established. These patterns occurred in both type I and type II diabetics independently of the duration of follow-up. This study has identified a pattern of intermittent microalbuminuria that is also associated with transient elevations of transferrin and IgG clearances. The relationship of clinical and biochemical parameters to proteinuria patterns was evaluated. No relationship was detected between proteinuria patterns and glycemic control in either type I or type II diabetics. In type I but not type II diabetics, established proteinuria was associated with higher systolic blood pressure and decreased creatinine clearance. The phase of intermittent proteinuria detected in this study may represent a reversible stage in the development of diabetic nephropathy, but the factors that trigger the transition to progressing proteinuria remain obscure.     

Conjunctival flora in patients with type 1 or type 2 diabetes mellitus

Patients with diabetes mellitus (DM) are prone to infection because glucose in the skin, urine, mucous membranes, and tears promotes growth of microorganisms. Conjunctival flora develops soon after birth, and some saprophytic conjunctival flora play a pathogenic role when immune function is compromised, which can lead to serious infection. DM is one condition that may compromise immune status. In lacrimal function tests of DM patients, a decrease in breakup time (BUT) of lacrimal film and a decrease in Schirmer’s test results were seen. In the present study, conjunctival flora in patients with DM was compared with that in controls with regard to type and duration of diabetes and results of lacrimal function tests. Seventeen patients with type 1 DM (n=34 eyes), 66 patients with type 2 DM (n=132 eyes), and 50 control subjects (n=100 eyes) were included. The control group consisted of age-matched patients with no ophthalmologic problems other than refractive error. Clycosylated hemoglobin values were measured with highpressure liquid chromatography with the Hi-AUTOA1c analyzer (Kyoto Daiichi Kagatu Co., Ltd., Kyoto, Japan). Type and duration of diabetes and demographic data were recorded, and routine ophthalmologic examinations were performed; the BUT of lacrimal film was determined, and the results of Schirmer’s test were assessed. Microbiologic sampling was performed twice for both eyes with sterile cotton swabs. One sample was incubated in 2 mL of brain-heart infusion broth agar; the other was incubated for the presence of fungi in Sabouraud dextrose agar. Colony morphology, hemolysis, and Cram’s stain, as well as catalase, oxidase, and coagulase tests were performed. No growth was observed in 12 of 1 7 patients (35.4%) with type 1 DM, 28 of 66 patients (21.2%) with type 2 DM, and 25 of 50 control subjects (50%).Staphylococcus epidermidis (11.79%) andStaphylococcus aureus (11.7%) were the most frequently isolated organisms in the type 1 DM group, and Sepidermidis (24.2%) and Saureus (21.2%) were the predominant organisms in the type 2 DM group. In control subjects, Sepidermidis (22%), Saureus (12%), andCorynebacterium spp (10%) were the most frequently isolated organisms, and the number of eyes with growth of Saureus was significantly higher in the type 2 DM group than in the other groups (P<.01). Patients with diabetes are more prone to postoperative endophthalmitis than are nondiabetics, and preoperative application of antiseptic or antimicrobial agents to the conjunctiva may not sterilize the area. Impaired integrity of the posterior capsule may also increase the risk of endophthalmitis. Postoperative endophthalmitis is usually associated with gram-positive organisms (75%–80%); gram-negative organisms (15%–29%) and fungi (3%–13%) account for a smaller number of cases. A high rate of resistance to penicillin, ampicillin, and tetracycline was observed in Saureus isolates, although resistance to vancomycin was absent, rendering this molecule the most effective therapeutic option. In this study, Sepidermidis and Saureus were the 2 most frequently isolated organisms in patients with DM. It is concluded that the conjunctival flora in diabetic subjects differs from that in nondiabetic subjects. This should be considered preoperatively and postoperatively, and prophylactic and postoperative treatment should be administered accordingly to diabetic patients.     

Pramlintide in the treatment of type 1 and type 2 diabetes mellitus

BACKGROUND: Amylin is a 37-amino acid peptide neurohormone that is cosecreted with insulin from the pancreatic beta cells in response to meals. It lowers serum glucose by decreasing glucagon release, slowing gastric emptying, and decreasing food intake. Pramlintide, a synthetic amylin analogue, is approved by the US Food and Drug Administration for use with mealtime insulin in patients with type 1 diabetes and patients with type 2 diabetes who are using mealtime insulin only or the combination of insulin and metformin and/or a sulfonylurea. OBJECTIVE: This article reviews the available literature on pramlintide with respect to its mechanism of action, pharmacokinetics and pharmacodynamics, clinical efficacy in type 1 and type 2 diabetes, safety and tolerability, dosing, contraindications, and drug interactions. METHODS: MEDLINE (1966-April 2005), Iowa Drug Information Service (1966-April 2005), and International Pharmaceutical Abstracts (1970-April 2005) were searched for clinical trials and therapeutic reviews published in the English language. The search terms were pramlintide and amylin. The bibliographies of identified articles were reviewed for additional references. All relevant studies were included in the review. RESULTS: Six studies, ranging in duration from 4 to 52 weeks, examined the effect of administering pramlintide with premeal insulin in patients with type 1 diabetes. In these trials, pramlintide 120 to 270 microg/d reduced glycosylated hemoglobin (HbA(1c)) by 0.1 % to 0.67%, 1-hour postprandial glucose (PPG) by 4.4 to 7 mmol/L, and 2-hour PPG by 3.6 to 4.8 mmol/L. Five studies, also ranging from 4 to 52 weeks' duration, examined the effect of administering premeal pramlintide in patients with type 2 diabetes. In these trials, pramlintide 90 to 450 microg/d reduced HbA(1c) by 0.3% to 0.62%, 1-hour PPG by 4.8 mmol/L, and 2-hour PPG by 3.4 mmol/L. The principal adverse events reported in clinical trials were nausea and hypoglycemia. The incidence of hypoglycemia in the first 4 weeks of therapy was 2 to 4 times greater with pramlintide compared with placebo; thus, the manufacturer recommends reducing the dose of premeal insulin by 50% when starting pramlintide. Close monitoring of blood glucose levels is recommended when initiating pramlintide therapy. CONCLUSIONS: Use of pramlintide in addition to insulin in patients with type 1 and type 2 diabetes was associated with modest reductions in HbA(1c). The primary adverse effects of pramlintide therapy were nausea and hypoglycemia.     

Basal C-peptide in the discrimination of type I from type II diabetes

Basal serum C-peptide concentrations in diabetic patients showed two groups. Diabetic patients with low C-peptide levels (less than or equal to 0.16 nmol/L) have clinical characteristics of type I diabetes, and all were on insulin therapy. With long duration of diabetes, an increasing proportion had undetectable C-peptide. Diabetic patients with high C-peptide levels (greater than 0.16 nmol/L) resemble type II diabetes. In this group 30% were on insulin therapy but duration of known disease was not associated with any decline in the high basal C-peptide levels. The small proportion of diabetic patients with basal serum C-peptide in the range of 0.17-0.32 nmol/L have indeterminate status.     

Insulin therapy in the management of type 1 and type 2 diabetes

This article describes the role of insulin therapy in the management of patients with type 1 and type 2 diabetes. It outlines the different types of insulin available, insulin regimens and the key role of nurses in patient education.     

Dyslipidemia in type 2 diabetes

Type 2 diabetes mellitus is associated with a cluster of lipid abnormalities:elevated plasma triglycerides, reduced high-density lipoprotein cholesterol, and smaller and denser low-density lipoproteins,which have been associated with an increased risk of cardiovascular disease. Insulin resistance may contribute to dyslipidemia associated with type 2 diabetes by increasing hepatic secretion of large,triglyceride-rich very low-density lipoprotein particles and by impairing the clearance of lipoprotein particles from plasma. Lifestyle interventions may be effective in improving the diabetic dyslipidemia syndrome. For patients who do not respond to lifestyle changes, pharmacologic therapies (lipid-lowering medications and anti-diabetic agents) are available. Clinical trials demonstrate that the use of such pharmaceutics to treat diabetic dyslipidemia concomitantly reduces the risk of coronary artery disease.     

Insulin therapy: optimizing control in type 1 and type 2 diabetes

Insulin has been available for therapeutic use for more than 75 years and remains a powerful pharmacologic tool with nearly unlimited potential to lower plasma glucose levels in patients with diabetes. Required essentially by all patients with type I diabetes and many patients with type 2 diabetes, insulin is capable of restoring near-normoglycemia—the primary treatment goal to forestall the onset and progression of long-term complications.Attainment and maintenance of near-normal glycemic control can be achieved with the use of insulin replacement strategies designed to simulate the physiologic, nondiabetic patterns of insulin secretion in response to 24-hour postabsorptive and postprandial glucose profiles. This article reviews the physiologic basis and current therapeutic agents for optimal insulin replacement and provides practical clinical guidelines and strategies to achieve near-normal glycemic control in patients with either type 1 or type 2 diabetes.     

Insulin therapy: optimizing control in type 1 and type 2 diabetes

Insulin has been available for therapeutic use for more than 75 years and remains a powerful pharmacologic tool with nearly unlimited potential to lower plasma glucose levels in patients with diabetes. Required essentially by all patients with type 1 diabetes and many patients with type 2 diabetes, insulin is capable of restoring near-normoglycemia--the primary treatment goal to forestall the onset and progression of long-term complications. Attainment and maintenance of near-normal glycemic control can be achieved with the use of insulin replacement strategies designed to simulate the physiologic, nondiabetic patterns of insulin secretion in response to 24-hour postabsorptive and postprandial glucose profiles. This article reviews the physiologic basis and current therapeutic agents for optimal insulin replacement and provides practical clinical guidelines and strategies to achieve near-normal glycemic control in patients with either type 1 or type 2 diabetes.     

Hypoglycemia in type 2 diabetes

Iatrogenic hypoglycemia is the limiting factor in the glycemic management of diabetes and a barrier to true glycemic control and becomes a progressively frequent clinical problem in advanced type 2 diabetes mellitus. As patients approach the insulin-deficient end of the spectrum of type 2, hypoglycemia results from the interplay of therapeutic insulin excess and compromised physiologic and behavioral defenses against falling plasma glucose concentrations.By practicing hypoglycemia risk reduction, applying the principles of aggressive glycemic therapy, and considering conventional risk factors and those indicative of compromised glucose counterregulation,it is possible to minimize the risk of hypoglycemia and improve glycemic control. Nonetheless, people with diabetes need better treatment regimens.     

Oxidative stress parameters in type I,type II and insulin-treated type 2 diabetes mellitus; insulin treatment efficiency

BACKGROUND: Our aim was to evaluate oxidative stress parameters on three groups of diabetic patients, insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM), and insulin-treated type 2 diabetes mellitus (ITDM2), with similar HbA1c value and to determine if insulin's impact on these parameters was the same for IDDM and ITDM2. METHODS: This study has been conducted on 18 IDDM, 55 NIDDM, 27 ITDM2, compared to 12 healthy subjects. Plasmatic concentrations of thiobarbituric acid reactive substances (TBARS), fatty acids, total antioxidant status (TAS), alpha-tocopherol, and erythrocyte reduced glutathione (GSH) were measured as well as enzymatic activities of superoxide dismutase (SOD), and glutathione peroxidase/reductase. RESULTS: Diabetic patients have significant increase of SOD activity, of TBARS concentration (concomitant with low levels of unsaturated fatty acids) and significant decrease of GSH and alpha-tocopherol. NIDDM have significantly lower levels of GSH and higher levels of TBARS compared to IDDM. ITDM2 values are intermediate between IDDM and NIDDM but are far from reaching those of IDDM. CONCLUSION: Diabetic patients undergo an important oxidative stress that is nearly corrected for IDDM, but only partially improved for ITDM2, although length of insulin treatment and HbA1c values are similar, suggesting metabolic differences between the two types of diabetes.     

Comparison of type I,type III and type VI collagen binding assays in diagnosis of von Willebrand disease

Summary. Background: von Willebrand factor (VWF) plays a key role in coagulation by tethering platelets to injured subendothelium through binding sites for collagen and platelet GPIb. Collagen binding assays (VWF:CB), however, are not part of the routine work‐up for von Willebrand disease (VWD). Objectives: This study presents data on collagen binding for healthy controls and VWD subjects to compare three different collagens. Patients/Methods: VWF antigen (VWF:Ag), VWF ristocetin cofactor activity and VWF:CB with types I, III and VI collagen were examined for samples obtained from the Zimmerman Program. Results: Mean VWF:CB in healthy controls was similar and highly correlated for types I, III and VI collagen. The mean VWF:CB/VWF:Ag ratios for types I, III and VI collagen were 1.31, 1.19 and 1.21, respectively. In type 1 VWD subjects, VWF:CB was similar to VWF:Ag with mean VWF:CB/VWF:Ag ratios for types I, III and VI collagen of 1.32, 1.08 and 1.1, respectively. For type 2A and 2B subjects, VWF:CB was uniformly low, with mean ratios of 0.62 and 0.7 for type I collagen, 0.38 and 0.4 for type III collagen, and 0.5 and 0.47 for type VI collagen. Conclusions: Normal ranges for type I, III and VI collagen are correlated, but higher values were obtained with type I collagen as compared with types III and VI. The low VWF:CB in type 2A and 2B subjects suggests that VWF:CB may also supplement analysis of multimer distribution. However, these results reflect only one set of assay conditions per collagen type and therefore may not be generalizable to all collagen assays.