Intensive Diabetes Treatment Research Articles

Diabetes and driving mishaps: frequency and correlations from a multinational survey.

The intensive treatment of diabetes to achieve strict glycemic control is a common clinical goal, but it is associated with an increased incidence of hypoglycemia. Becoming hypoglycemic while driving is a hazardous condition and may lead to a greater incidence of driving mishaps. This study investigated whether diabetes is associated with increased risk of driving mishaps and correlates of such a relationship. During routine visits to diabetes specialty clinics in seven U.S. and four European cities, consecutive adults with type 1 diabetes, type 2 diabetes, and nondiabetic spouse control subjects (n = 341, 332, and 363, respectively) completed an anonymous questionnaire concerning diabetes and driving. Type 1 diabetic drivers reported significantly more crashes, moving violations, episodes of hypoglycemic stupor, required assistance, and mild hypoglycemia while driving as compared with type 2 diabetic drivers or spouse control subjects (P < 0.01-0.001). Type 2 diabetic drivers had driving mishap rates similar to nondiabetic spouses, and the use of insulin or oral agents for treatment had no effect on the occurrence of driving mishaps. Crashes among type 1 diabetic drivers were associated with more frequent episodes of hypoglycemic stupor while driving, less frequent blood glucose monitoring before driving, and the use of insulin injection therapy as compared with pump therapy. One-half of the type 1 diabetic drivers and three-quarters of the type 2 diabetic drivers had never discussed hypoglycemia and driving with their physicians. Type 1 diabetic drivers are at increased risk for driving mishaps, but type 2 diabetic drivers, even on insulin, appear not to be at a higher risk than nondiabetic individuals. Clinical and treatment factors appear to increase risk, e.g., more frequent hypoglycemia while driving, method of insulin delivery, and infrequent self-testing before driving. Physicians are encouraged to talk to their type 1 diabetic patients about hypoglycemia and driving.

Köbberling type of familial partial lipodystrophy: an underrecognized syndrome.

The phenotypic expression of partial lipodystrophy is present in two familial syndromes: familial partial lipodystrophy type 1 (FPLD1), with fat loss from the extremities, and central obesity and FPLD type 2, with fat loss from the extremities, abdomen, and thorax. The latter disorder is associated with mutations in the LMNA gene. FPLD1 is thought to be rare. Here, we report 13 subjects with FPLD1, suggesting that this syndrome is more common than previously thought. Fasting glucose, plasma lipids, leptin, HbA(1c), and anthropomorphic measurements were evaluated in 13 subjects with clinical features of FPLD1 and are compared with two age-matched control groups, with and without diabetes. Only women with clinical features of FPLD1 have been identified. Although they lack extremity and gluteal subcutaneous fat, they do have truncal obesity. Skinfold thickness on the arm and leg was significantly less than that in control subjects. The ratio of skinfold thickness from abdomen to thigh was significantly higher in subjects, suggesting an easy method for identifying affected patients. FPLD1 subjects also had components of the metabolic syndrome, including hypertension, insulin resistance, and severe hypertriglyceridemia resulting in pancreatitis. Premature coronary artery disease was present in 31% of subjects. None of the subjects had coding mutations in the LMNA gene or in the gene coding for peroxisome proliferator-activated receptor (PPAR)-gamma. FPLD1 is more common than previously described, but the diagnosis is often missed. Early recognition and intensive treatment of hyperlipidemia and diabetes in FPLD1 is important for prevention of pancreatitis and early cardiovascular disease.

Association of hypoglycemia and cardiac ischemia: a study based on continuous monitoring.

In some studies intensive diabetes treatment in patients with type 2 diabetes may be associated with increased cardiovascular events. It is not clear whether these events are related to hypoglycemic episodes. To determine whether episodes of hypoglycemia were more likely to be associated with cardiac ischemia than normoglycemia or hyperglycemia, we carried out a study in 21 patients with coronary artery disease (CAD) and type 2 diabetes treated with insulin who had good glycemic control. We carried out 72-h continuous glucose monitoring along with simultaneous cardiac Holter monitoring for ischemia. Patients also recorded symptoms of cardiac ischemia (chest pain) and symptoms of hypoglycemia. Satisfactory continuous glucose monitoring system recordings were obtained in 19 patients. We recorded 54 episodes of hypoglycemia (blood glucose <70 mg/dl; 26 of these were symptomatic) and 59 episodes of hyperglycemia (blood glucose >200 mg/dl; none symptomatic). Of the 54 episodes of hypoglycemia, 10 were associated with symptoms of chest pain, during 4 of which electrocardiographic abnormalities were documented. In contrast, only 1 episode of chest pain occurred during 59 episodes of hyperglycemia. No chest pain or electrocardiographic abnormalities occurred when the blood glucose was within the normal range. The difference between the frequency of ischemia during hypoglycemia and the frequency during both hyperglycemia and normoglycemia was statistically significant (P < 0.01). There were 50 episodes during which the blood glucose changed by >100 mg over a 60-min period, and ischemic symptoms occurred during 9 of these episodes (P < 0.01 compared with stable normoglycemia or hyperglycemia). Hypoglycemia is more likely to be associated with cardiac ischemia and symptoms than normoglycemia and hyperglycemia, and it is particularly common in patients who experience considerable swings in blood glucose. These data may be important in the institution of insulin treatment and attempting near-normal glycemia in patients with known CAD. Further research is needed to determine strategies to prevent ischemia associated with hypoglycemia.

糖尿病とリハビリテーション

Function of carbohydrate metabolism is clinically classified as normal, impaired glucose tolerance (IGT), non-insulin dependent diabetes, insulin dependent diabetes and brittle diabetes. According to ICF, their function may be expressed as b540.0, b540.1, b540.2, b540.3 and b540.4, respectively. Their structure may be also expressed as s550.000, s550.189, s550.229, s550.329, s550.419, respectively. Diabetes mellitus is an important risk factor of many kinds of disability such as heart failure, mobility disability due to stroke, renal failure, and blindness. The effect of intensive diabetes treatment on long-term complications was confirmed in insulin dependent diabetes by DCCT Research Group, and in non-insulin dependent diabetes by UK Prospective Diabetes Study Group and Kumamoto Study. Based on these evidences, clinical recommendation of diabetes treatment was proposed by Japan Diabetes Society. Purpose of diabetes rehabilitation is maintaining their healthy condition without complications and supports them in minimizing activity limitation and participation restriction due to diabetes. In diabetes rehabilitation, it is very important to teach them on the principle of treatment of diabetes, diabetic complications and realizable methods of self-care, in detail.

Hypoglycaemic neuropathy: microvascular changes due to recurrent hypoglycaemic episodes in rat sciatic nerve

Intensive diabetes treatment causes a considerable increase in the number of severe hypoglycaemic episodes which could aggravate the progression of diabetic neuropathy. However, the effect of repeated hypoglycaemic episodes on nerve morphology has never been previously investigated. The aims of the present study were: (i) to establish a rat model of recurrent episodes of severe hypoglycaemia, and (ii) to assess morphological changes after repeated hypoglycaemic episodes in rat sciatic nerves. We induced hypoglycaemic episodes, blood glucose level <3.0 mmol/l for 3 h, by injecting regular insulin intravenously on 4 consecutive days. We found endothelial swelling of endoneurial microvessels at the thigh level of sciatic and tibial nerves 24 h after four daily episodes of hypoglycaemia. Endothelial swelling was confirmed by vascular morphometry which showed significantly increased endothelial and pericyte areas. No obvious abnormalities were seen on nerve fibres. In conclusion, recurrent hypoglycaemic episodes cause early vascular anomalies in endoneurial microvessels in rat sciatic nerves without any observable changes in nerve fibres.

DiasNet—a diabetes advisory system for communication and education via the internet

Intensive diabetes treatment can lead to a substantial reduction of the rate of the complications associated with diabetes. However, a number of patients may have poor control despite specialist care, and this along with devolution of care to non-specialists suggests that alternative interventions should be developed. The present paper describes an Internet based system where more emphasis is put on patient empowerment, the keywords being education and communication. The DiasNet system is based on a well documented decision support system, Dias, designed for use by clinicians. The scope of DiasNet has been widened from being used by clinicians to give advice on insulin dose, to also being used by patients as a tool for education and communication. Patients can experiment with their own data, adjusting insulin doses or meal sizes. In this way different therapeutic and dietary alternatives can be tried out, allowing the patient to gain experience in achieving glycaemic control. DiasNet is implemented in JAVA according to the client/server principle, enabling a new way of communication between patient and clinician: in case of any problems, the patient simply phones the clinician, who immediately, using his or her office PC, can take a look at the data the patient has entered.

Searching for glycemic control in pediatric type 1 diabetes: A long way to go

Searching for glycemic control in pediatric type 1 diabetes: A long way to go

Psychosocial and quality of life correlates of glycemic control during intensive treatment of type 1 diabetes

To identify emotional and attitudinal barriers to improved glycemic control (HbA 1c) during intensive diabetes treatment, 55 patients attending a 4–5 month intensive diabetes medical/education clinic were followed. Subjects completed a battery of psychological surveys, had HbA 1c and body mass index measured, and rated their attitude toward weight gain and the extent of problems with specific self-management behaviors before and after the medical intervention. Although HbA 1c improved on average, 29% had only modest improvement and 16% showed no improvement. The number of diabetes-related annoyances, worry about hypoglycemia, and diabetes-related emotional distress diminished. Only the satisfaction subscale of the Diabetes Quality of Life survey, diabetes-related emotional distress, and problems with self-management behaviors correlated with HbA 1c. Treatment-related frustration and emotional distress may initially act as motivators to improve glycemia but can later become barriers to that goal. Interventions designed to help patients overcome attitudinal barriers should be incorporated into medical programs geared toward improving glycemia.

Evaluation of glomerular lesions in diabetes mellitus

Evaluation of glomerular lesions in diabetes mellitus

Malignant disease and the adolescent.

11 Steel JM. Eating disorders. In: Kelnar CJH (ed). Childhood and adolescent diabetes. London: Chapman and Hall, 1995: 375–84. 12 Fosbery J, Moore S, Kidd J, Sonksen PH, Amiel S. Psychological issues in the diabetic clinic. Pract Diabetes Int 1996; 12:92–3. 13 Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329:977–86. 14 Carson C. Innovative approach to improving care for diabetic adolescents. J Diabetes Nurs 1998;2:108–11.

Diabetes in Oman: Comparison of 1997 American Diabetes Association Classification of Diabetes Mellitus with 1985 WHO Classification

Diabetes mellitus (DM) is a major public health problem in Oman. We evaluated the impact of the revised diagnostic criteria for DM adopted by the American Diabetes Association (ADA) on the prevalence of diabetes and impaired glucose tolerance (IGT), and on the classification of individuals among the Omani population. We used the dataset of the National Diabetes Survey, conducted in 1991 and involving 4682 subjects who did not have any missing data on fasting and 2-hour glucose. The subjects comprised 2002 males and 2680 females aged 20 years or above. Data were analyzed using the ADA criteria (diabetes as fasting plasma glucose [FPG] > or =7 mmol/L, impaired fasting glucose [IFG] as FPG > or =6.1 mmol/L and <7 mmol/L), and compared these with the World Health Organization (WHO) criteria (diabetes as FPG > or =7.8 mmol/L and/or 2-hour post-glucose load > or =11.1 mmol/L, IGT as FPG <7.8 mmol/L, and 2-hour post-load 7.8-11.1 mmol/L). Applying the ADA criteria on the Omani population resulted in an overall reduction of diabetes prevalence by 2.2% (95% confidence interval [CI] 1.6% to 2.8%), and a 4.8% reduction of IGT (95% CI 3.8% to 5.8%). Over 29% of diabetics classified by the WHO criteria were reclassified as being normal or having IFG by the ADA criteria. Around 3.6% of those who were normoglycemic by the WHO criteria were classified as having diabetes or IFG by the ADA criteria. In all but one region of Oman, the prevalence of diabetes and IFG using the ADA criteria was lower compared to the prevalence using the WHO criteria. Gender, age and body mass index did not seem to pose an increased risk to the probability of being diagnosed by one criteria or the other or both together. The adoption of the ADA criteria in Oman will significantly reduce the prevalence of diabetes and IGT. In addition, the glycemic status of a substantial number of individuals will be changed from normal to either being diabetic or having IGT.

Pattern and Factors Associated with Glycemic Control of Saudi Diabetic Patients

The pattern and factors which can be associated with the glycemic control of Saudi adult diabetic patients were examined in this study. Confirmed diabetic patients from all regions of Saudi Arabia constituted the study population. Random blood glucose <10 mmol/L and >10 mmol/L was used to categorize patients into good and poor glycemic control patients, respectively. There were 613 confirmed non-insulin dependent diabetic patients (NIDDM), 50% with good glycemic control. Patients with poor glycemic control were significantly older than patients with good glycemic control (51.5 vs. 47 years, P=0.0001). The insulin-treated diabetic population amounted to 13%, compared with 43% and 44% for oral agent and diet, respectively. The rate of insulin users among poor glycemic control diabetic population was 18%, compared with 50% for oral agents. There was a significant relationship between glycemic control and age, and treatment modalities of DM. Subjects who had good glycemic control of DM were younger and following a diet regimen, while those who had poor glycemic control were older and on insulin treatment. Multivariate analysis comprising 415 individuals was conducted to find out the factors that can potentially influence, or may be associated with, the control of DM. The association of insulin therapy with poor glycemic control is not a cause-effect relationship. Insulin therapy in our study population is underutilized, given the high rate of poor glycemic control and high rate of relative occurrence of complication among the Saudi diabetic population. There is a need to address the importance of maintaining good glycemic control, and the reason for the low rate of insulin users. Close periodic monitoring of glycemic control, utilizing laboratories and home glucose monitoring devices, is required. Effective implementation of these measures, in addition to diabetes education, will have an impact on the future outcome of the Saudi diabetic population.

Feasibility of Applying Recommendations from the Diabetes Control and Complications Trial to Saudi Adolescents with Insulin-Dependent Diabetes

Feasibility of Applying Recommendations from the Diabetes Control and Complications Trial to Saudi Adolescents with Insulin-Dependent Diabetes

Resistance to Neuroglycopenia: An Adaptative Response during Intensive Insulin Treatment of Diabetes

Resistance to Neuroglycopenia: An Adaptative Response during Intensive Insulin Treatment of Diabetes

Cost drivers in diabetes care: the problems they present and potential solutions

Diabetes mellitus is a chronic disease that affects many aspects of the lives of diagnosed patients and their families, the health care industry, and society. The majority of the economic literature on diabetes addresses the cost of treating diabetes but not the outcomes of clinical interventions. The primary cost of treating diabetes is related to short-term care to achieve euglycemia and long-term care associated with complications of the disease. The short-term costs of achieving euglycemia can be overshadowed by the decreased risk of long-term complications. The difficulty of providing care for a chronic disease such as diabetes arises from the high short-term costs of clinical interventions, the positive benefits of which may not be realized for many years. The results of the Diabetes Control and Complications Trial show a correlation between the intensive treatment of diabetes and a decreased risk of the development of long-term complications. Whether intensive treatment is practical, effective, and cost-effective in a real-world setting is a topic for further study. In the meantime, health care providers with a good knowledge of the clinical and economic elements of available therapeutic options can develop individualized care regimens for their patients with diabetes that are high quality and cost-effective

Time to Declare War on Diabetes

Time to Declare War on Diabetes

Exogenous insulin administration and cardiovascular risk in non-insulin-dependent and insulin-dependent diabetes mellitus.

It is currently unknown whether intensive insulin treatment of diabetes decreases the risk for cardiovascular complications by lowering glucose levels or increases the risk by postulated direct atherogenic effects. This article reviews published data from two long-term, randomized clinical trials that compared cardiovascular outcomes associated with different exogenous insulin treatment regimens. STUDY SELECTION AND DATA SOURCES: The University Group Diabetes Program (UGDP) and the Diabetes Control and Complications Trial (DCCT) were selected as the only available randomized intervention trials with long-term follow-up results. Data reviewed were from the major publications of these two trials. The UGDP compared the effects of a fixed-dose standard insulin regimen, a variable-dose insulin regimen, and a diet plus oral placebo regimen in over 600 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were followed for up to 13 years (1962 to 1975). Plasma glucose levels were 1.7 to 2.2 mmol/L lower in the variable-dose insulin regimen group than in the other two treatment groups. No significant differences were found in the final prevalence or the cumulative incidence of total deaths, cardiovascular disease deaths, or myocardial infarctions among the three treatment groups, even when outcomes were adjusted for pertinent baseline cardiovascular risk factors. There was a slight suggestion only from post hoc analysis that patients in both insulin treatment groups, who were defined as having good glucose control, had fewer cardiovascular events than those with fair or poor control. The DCCT compared intensive insulin treatment with conventional insulin treatment (the mean hemoglobin A1c [HbA1c] level was 7.2% and 9.0%, respectively) in over 1400 patients with insulin-dependent diabetes (IDDM) followed for up to 10 years (1983 to 1993). Three major cardiovascular events occurred in the intensive treatment group as compared with 14 in the conventional treatment group (P > 0.05), and low-density lipoprotein cholesterol and triglyceride levels were substantially lower in the intensive treatment group. However, body mass index increased substantially more with intensive than with conventional therapy. The UGDP trial was flawed by inadequate power, insufficient separation of glycemic levels, and ignorance of smoking history as a possible confounder. In the DCCT, the number of cardiovascular events was few because the patients were young and had a relatively short duration of diabetes at baseline. In addition, total daily insulin doses were similar in the two DCCT treatment groups. For these reasons, neither trial provides a definitive answer to the question about the effects of intensive insulin therapy. A better designed clinical trial is needed to determine whether insulin treatment has beneficial or adverse effects, or even offsetting beneficial and adverse effects, on the risk for cardiovascular disease in NIDDM and IDDM.

The Pathophysiology of Diabetic Complications: How Much Does the Glucose Hypothesis Explain?

To examine the putative pathogenetic mechanisms of the long-term, specific complications of diabetes mellitus. Literature review relevant to long-term diabetic complications and their pathogenesis. Studies of animal models of diabetes, epidemiologic investigations of diabetes and its long-term complications, and interventional studies examining intensive treatment of diabetes and its effect on the development and progression of complications. Diabetic retinopathy, nephropathy, and neuropathy occur in all clinical forms of diabetes mellitus, regardless of the cause of the diabetes. Hyperglycemia appears to be the major variable shared among these different clinical forms; and epidemiologic data, studies in animal models of diabetes, and the results of recent interventional studies such as the Diabetes Control and Complications Trial, all support an important and perhaps dominant role of hyperglycemia in the pathogenesis of complications. However, the diverse complications may not share the same pathogenesis. Different pathogenetic mechanisms may operate in different types of diabetic complications or at different stages of specific complications, or both. The level of chronic glycemia is the best established concomitant factor associated with diabetic complications. The mechanism by which hyperglycemia might cause complications remains unknown, and evidence for a uniform pathogenetic mechanism is far from established.

Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial

The Diabetes Control and Complications Trial (DCCT) has demonstrated that intensive diabetes treatment delays the onset and slows the progression of retinopathy, nephropathy, and neuropathy in patients with IDDM. A detailed description of the effects of this treatment on diabetic nephropathy is presented here. In the primary prevention cohort, intensive treatment reduced the mean adjusted risk of the cumulative incidence of microalbuminuria (> or = 28 micrograms/min) by 34% (95% CI 2, 56%; P = 0.04). Furthermore, intensive treatment decreased the albumin excretion rate (AER) by 15% after the first year of therapy (6.5 vs. 7.7 micrograms/min, P < 0.001). Thereafter the rates of change for AER within each treatment group were no different from zero, retaining a constant difference in AER between groups in the trial. In the secondary intervention cohort with baseline AER < 28 micrograms/min, intensive therapy reduced the mean adjusted risk of microalbuminuria (> or = 28 micrograms/min) by 43% (95% CI 21, 58%; P < 0.0001); the risk of a more advanced level of microalbuminuria (> or = 70 micrograms/min) by 56% (95% CI 26, 74%; P = 0.002); and the risk of clinical albuminuria (> or = 208 micrograms/min) by 56% (95% CI 18, 76%; P < 0.01). In the secondary intervention cohort, values for AER at year 1 were identical at 9 micrograms/min, but the 6.5% change per year in the conventional group greatly exceeded the rate of change of -0.3% in the intensive group (P < 0.001). Among the 73 secondary cohort subjects with AER levels > or = 28 micrograms/min but < or = 139 micrograms/min at baseline, the reduction of progression to clinical albuminuria with intensive therapy was not statistically significant. The longitudinal treatment effect of conventional versus intensive therapy (11.0% vs. 2.5% per year, respectively, P = 0.087) was similar in magnitude to that among patients with AER < 28 micrograms/min at baseline. For the primary, secondary and combined cohorts, there were no significant differences in the rates of change in creatinine clearance (CCr) between treatment groups during the study. Only seven subjects in the entire study (2 intensive, 5 conventional) developed urinary AER > or = 208 micrograms/min coupled with a CCr < 70 ml/min/1.73 m2. Neither the rate of change of blood pressure nor the appearance of hypertension (BP > 140/90 mm Hg) differed significantly between treatment groups in the primary, secondary or combined cohorts.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of intensive diabetes management on macrovascular events and risk factors in the diabetes control and complications trial

The Diabetes Control and Complications Trial (DCCT), a multicenter, randomized, controlled clinical trial, demonstrated that intensive diabetes therapy delays the onset and slows the progression of retinopathy, nephropathy, and neuropathy in patients with insulin-dependent diabetes mellitus. This study presents the effect of intensive therapy on atherosclerosis-related events and associated risk factors. Patients (n = 1,441) between the ages of 13 and 39 years with insulin-dependent diabetes mellitus were randomly assigned to conventional or intensive diabetes treatment. The patients were free of cardiovascular disease at baseline. Patients with hypertension, hypercholesterolemia, or obesity were excluded. Average length of follow-up was 6.5 years (range 3.5 to 9). The study used standardized definitions of macrovascular events, verification of such events, and central laboratories for determination of lipids and the grading of electrocardiograms. The number of combined major macrovascular events was almost twice as high in the conventionally treated group (40 events) as in the intensive-treatment group (23 events), although the differences were not statistically significant (p = 0.08). There were no differences in the cumulative incidence of hypertension. Mean total serum cholesterol, calculated low-density lipoprotein cholesterol, and triglycerides were significantly reduced in the intensive-treatment group (p < or = 0.01), as was the development of low-density lipoprotein cholesterol levels > 160 mg/dl. Weight gain was significantly increased in the intensive-treatment group (p < 0.001). There were no differences in cigarette smoking habits, consumption of alcohol, or aspirin use between treatment groups. The reduction in some, but not all, cardiovascular risk factors suggests a potential beneficial effect of intensive therapy on macrovascular disease in insulin-dependent diabetes mellitus.