Diabetic nephropathy and end-stage renal disease in Mexican Americans

Hispanics are the second largest minority group in the United States. Mexican Americans (MAs) are the largest subgroup at 14 million in 1990. MAs have a two- to threefold increased prevalence of non-insulin-dependent diabetes mellitus. Population-based studies of MAs with non-insulin-dependent diabetes have shown that these patients may be more likely than non-Hispanic whites to develop proteinuria and are more likely to develop end-stage renal disease. The reasons for this excess risk are yet to be completely elucidated, but may be due to worse glycemic control, worse blood pressure control when hypertension does occur, worse access to medical care, and/or genetics. When MAs are treated for diabetic end-stage renal disease, they have better survival. Much less data are available for other Hispanic subgroups. From a public health perspective, higher incidence and longer survival as well as relatively young and rapidly growing population predict an increasing burden for MAs if prevention measures are not instituted soon.     

Issues surrounding tight glycemic control in people with type 2 diabetes mellitus

OBJECTIVE: To review the prospective evidence surrounding the issue of tight glycemic control in people with type 2 diabetes mellitus and resultant long-term complications. DATA SOURCE: Conference proceedings and a MEDLINE search (1966-February 1998) identified pertinent English-language publications on type 2 diabetes in humans. Key search terms included insulin resistance, diabetes mellitus, non-insulin-dependent, macrovascular complications, microvascular complications, and intensive glycemic control. STUDY SELECTION: Selection of prospective epidemiologic and clinical studies were limited to those focusing on the management of type 2 diabetes. All articles with pertinent information relevant to the scope of this article were reviewed. DATA SYNTHESIS: The pathophysiology of type 1 and type 2 diabetes differ; however, both share chronic complications that significantly affect morbidity and mortality. People with type 1 diabetes have an absolute deficiency of insulin, whereas people with type 2 diabetes have varying degrees of insulin resistance and an inadequate compensatory insulin secretory response. The Diabetes Control and Complications Trial (DCCT) has clearly indicated that intense control of blood glucose in type 1 diabetes prevents and slows the progression of microvascular (i.e., retinopathy, nephropathy) and neuropathic complications. The Kumamoto study showed similar results in nonobese patients with type 2 diabetes. Intense insulin therapy in both populations has proven advantageous, thus supporting a common pathophysiologic process for the microvascular and neuropathic complications. Trends were seen toward fewer macrovascular (atherosclerotic disease) complications in the intensive insulin arm of the DCCT. Conversely, trends were seen toward an increase in macrovascular complications in the VA Cooperative study in people with type 2 diabetes using intensive insulin therapy. This may suggest a discordance in the pathophysiology of macrovascular disease between type 1 and type 2 diabetes. Additionally, it remains uncertain whether tight glycemic control prevents the onset or slows the progression of macrovascular disease. Two studies (the University Group Diabetes Program and the Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type 2 Diabetes) to date have examined pharmacotherapy options for patients with type 2 diabetes and resultant macrovascular complications. It has yet to be determined whether any therapeutic intervention will decrease the morbidity and mortality of macrovascular disease in this population. CONCLUSIONS: In type 2 diabetes, limited prospective evidence does support tight glycemic control to help prevent or slow the progression of microvascular and neuropathic complications. It is uncertain whether tight glycemic control decreases macrovascular complications and which pharmacotherapeutic agent(s) is/are the best options. However, therapy that improves glucose control in combination with aggressive risk factor management should be initiated and enforced in patients with type 2 diabetes in an effort to reduce long-term complications.     

Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study

OBJECTIVE: Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications. RESEARCH DESIGN AND METHODS: In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28-40 kg/m2, and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured. RESULTS: After 1 year of treatment, the orlistat group lost 6.2 +/- 0.45% (mean +/- SEM) of initial body weight vs. 4.3 +/- 0.49% in the placebo group (P < 0.001). Twice as many patients receiving orlistat (49 vs. 23%) lost > or = 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA1c (P < 0.001) and fasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P < 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients. CONCLUSIONS: Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile.     

Long-term glycemic control influences the onset of limited joint mobility in type 1 diabetes

BACKGROUND: Limited joint mobility (LJM) in childhood insulin-dependent (type 1) diabetes is associated with a substantially increased risk of microvascular complications. Cross-sectional studies have not demonstrated a relationship between LJM and metabolic control. This study was designed to determine whether glycemic control, as measured by glycohemoglobin (hgbA1C) levels from the onset of diabetes, is associated with the occurrence of LJM. METHOD: Probands (n = 18) had hgbA1C values and recorded observation of joint function from soon after onset of their diabetes. Controls (n = 40) were matched to probands for gender and age at diagnosis and had follow-up beyond the age at which the proband was found to have LJM. RESULTS: The odds ratio for occurrence of LJM for the mean hgbA1C from diabetes onset was 1.46, 95% confidence limits 1.07 to 2.00. Thus, for every unit increase in average hgbA1C, there was approximately a 46% increase in the risk of LJM. When hgbA1C was dichotomized, the OR for hgbA1C of more than 8% was 2.55, and the OR was 4.54 if the hgbA1C was greater than 12%. Age at diagnosis and duration of diabetes were not independent prognostic factors for LJM. CONCLUSION: Glycemic control from onset of diabetes is strongly associated with occurrence of LJM.     

Fatal attraction: do high-technology treatments for end-stage renal disease benefit aboriginal patients in central Australia?

The health problems of Aboriginal Australians, like those of many indigenous peoples, resemble those of the developing world, yet they are dealt with using the tools, techniques, and high-technology medical solutions of first-world health. Such approaches ignore the social components of health and illness, including the need for preventive and educative programs at the primary health care level. The example of endstage renal disease provides a poignant example of the inadequacies of this approach. Central Australian Aboriginal people suffer from a high incidence of kidney disease from numerous causes including non-insulin-dependent diabetes mellitus and glomerulonephritis. The high incidence has led to numbers of people developing end-stage renal disease and moving into the Northern Territory-South Australia renal failure program for dialysis and/or transplantation. In requiring patients to leave their lands, communities and families, this program removes people from the religious and social support network that could ensure a reasonable quality of life in their final years, while offering only marginal extensions of those years. Expensive technology programs are of little benefit and of considerable cost to Aboriginal patients and draw attention away from efforts to reduce the exposure of at-risk Aboriginal people to the factors that facilitate the development of end-stage renal disease.     

Consequences of irregular versus continuous medical follow-up in children and adolescents with insulin-dependent diabetes mellitus

OBJECTIVES: To study the social and family characteristics of patients with insulin-dependent diabetes mellitus with irregular versus continuous clinical follow-up and to study the medical outcomes of patients with these follow-up patterns. METHODS: An onset cohort of 61 children and adolescents with insulin-dependent diabetes mellitus and their parents were studied. Aspects of their social and family environment were assessed at study inception and examined in relation to frequency of follow-up early in the course of the illness. Follow-up was dichotomized so that patients with continuous follow-up were compared with patients with irregular follow-up, who were defined as those missing 1 full year of planned medical appointments during the second through fourth years after diagnosis. Patients with irregular and continuous follow-up were compared in terms of acute metabolic complications, glycemic control, and retinopathy status during a 10-year period. RESULTS: Compared with individuals with continuous follow-up, patients with irregular clinical visits were more likely to be from families of lower socioeconomic class levels, have a parental history of separation and divorce, and were members of families that reported being least openly expressive of positive emotions. Poor glycemic control in year 1 was associated with irregular follow-up in years 2 through 4. Patients with irregular follow-up continued to have worse glycemic control in years 2 through 4 than patients with continuous follow-up. However, in years 7 and 10 their glycemic control no longer differed from patients with continuous follow-up. More episodes of diabetic ketoacidosis occurred in the irregular follow-up group. Finally, retinopathy occurred more frequently among those in the irregular follow-up group. CONCLUSION: Early irregular clinical follow-up should be considered a risk factor for complications of insulin-dependent diabetes mellitus.     

Self-care behaviors, self-efficacy, and social support effect on the glycemic control of patients newly diagnosed with non-insulin-dependent diabetes mellitus

The purpose of this study was to explore the glycemic control and influencing factors in outpatients newly diagnosed with non-insulin-dependent diabetes mellitus (NIDDM). By purposeful sampling, data were collected from 130 outpatients with NIDDM at one medical center in Kaohsiung. The results indicated: (1) the mean value for HbA1C was 7.12%; and 63.1% of the patients belonged to moderate to well controlled group; (2) male patient's HbA1C value was significantly lower than female patient's; patients with no religious belief also had a lower HbA1C value than patients with a religious background; (3) there were strongly negative correlations between self-care behaviors, social support, and self-efficacy and HbA1C; (4) using a multiple stepwise regression analysis, religious belief and self-care behaviors were found to explain 10.9% variance of HbA1C level. The results of this study could be used as a reference for diabetes health education program.     

Long-term glycemic control has a nonlinear association to the frequency of background retinopathy in adolescents with diabetes. Follow-up of the Berlin Retinopathy Study

OBJECTIVE: To assess the influence of long-term glycemic control on the development of background retinopathy in adolescents followed longitudinally from the onset of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Repeated retinal fluorescein angiographies, in intervals of 1-2 years, were evaluated prospectively in 346 patients (190 males, 156 females; 19.8 [8.8-35.4] years of age; diabetes duration of 10.4 [1.1-27.4] years at their latest eye examination, median [range]). The influences of long-term HbA1c (mean of 18 [1-95] determinations per person) and microalbuminuria (> or = 2 of > or = 3 measurements > or = 15 micrograms/min x 1.73 m2) were studied by multiple linear regression, life-table analysis, and trend analyses. RESULTS: The rate of background retinopathy per 100 patient-years increased with poorer glycemic control from 0.7 (long-term HbA1c < 7% to 7.3 (HbA1c > 11%) following an exponential function. Life-table analysis after subdivision in HbA1c quartiles of equal sizes (HbA1c < 8, 8-9, 9-10, and > 10%) revealed an individual median expectation of background retinopathy after more than 25, 16.2, 12.7, or 12.0 years of diabetes, respectively. However, significant differences were found only between 8-9% and 9-10%, calculated either as prevalence, life-table analysis, or relative incidence, thus suggesting that a threshold model may also fit the data. After 12 years of diabetes, < 25% of those patients exhibiting microalbuminuria (n = 18) were expected to be free from retinopathy compared with 81% of those with normoalbuminuria (n = 86). CONCLUSIONS: Two statistical models are appropriate to explain the relationship between glycemic control and risk for background retinopathy: 1) a continuous exponential relationship as described by the DCCT or 2) the presence of a threshold HbA1c level at 9%. Thus, diabetes treatment in children should aim at long-term HbA1c levels < 9.0%, but every progress closer to normal may further reduce the risk.     

Recent advances in the treatment of type II diabetes mellitus

Diabetes mellitus needs to be managed early to prevent the onset and progression of complications. Diet and exercise may not be sufficient to achieve and maintain good glycemic control. Currently, no pharmacologic agent addresses all of the fundamental abnormalities in the pathogenesis of type II diabetes mellitus. However, the newer agents do not exacerbate the hyperinsulinemia that often occurs with type II diabetes, and they may help reduce the risk of cardiovascular disease that is associated with high insulin levels. Two of these agents, metformin and acarbose, have recently become available in the United States for the treatment of type II diabetes. With the availability of agents that differ in their mechanisms of action and side effect profiles, regimens can be individualized to address the variety of pathophysiologic abnormalities in type II diabetes. For this purpose, agents can be used alone or in combination.     

Biomedical and psychiatric risk factors for retinopathy among children with IDDM

OBJECTIVE: Illness duration and glycemic control influence the development of retinopathy in childhood-onset insulin-dependent diabetes mellitus (IDDM). Psychiatric disorders and sociodemographic factors also affect diabetes-related outcomes. However, biomedical and psychosocial factors have not been examined together in modeling the risk of retinopathy. RESEARCH DESIGN AND METHODS: We conducted a single-site prospective longitudinal study of 66 children (aged 8-13 years) newly diagnosed with IDDM. Repeated assessments served to derive psychiatric diagnoses. Poor glycemic control was defined as the upper 15th percentile of all HbA1 values. After a median follow-up of 10 years, severity of retinopathy was determined. It was modeled with a stepwise polychotomous regression procedure using antecedent biomedical and psychosocial variables. RESULTS: Young adults with childhood-onset IDDM were found to be at increased risk of retinopathy the longer they had IDDM, the more persistently they evidenced poor antecedent glycemic control, and the longer they suffered from depressive illness. These three factors operated individually and additively, with duration of IDDM conferring a baseline level of risk. In depressed patients (27%), depression onset antedated the detection of retinopathy generally by 7 years. CONCLUSIONS: Duration of childhood-onset IDDM confers a baseline level of risk of retinopathy irrespective of glycemic control; antecedent clinical depression is also a risk factor. Depression therefore may serve as a marker of vulnerability and help to identify a subgroup of patients at risk for complications. The findings raise the question whether timely treatment of depression could forestall diabetic retinopathy.     

Retinopathy and vision loss in insulin-dependent diabetes in Europe. The EURODIAB IDDM Complications Study

PURPOSE: To assess the frequency of retinopathy and vision loss in patients with insulin-dependent diabetes mellitus and their relations to potentially modifiable risk factors. METHODS: The authors conducted a multicenter cross-sectional study of diabetic complications and their risk factors using standardized methods of assessment. The sample was comprised of 3250 insulin-dependent diabetic patients (1668 men, 1582 women) aged 15 to 60 years with mean (standard deviation) duration of diabetes of 14.7 (9.3) years from 31 European diabetes centers; 2991 of the patients were eligible for retinal photography. Visual acuity was measured using the Snellen chart. Retinopathy was evaluated by retinal photographs (two fields per eye) graded at a central facility. Glycated hemoglobin (HbA1c), cholesterol, triglyceride, fibrinogen, von Willebrand factor, and urinary albumin excretion rate were assessed at a single location. RESULTS: Corrected visual acuity was greater than or equal to 1.0 in both eyes in 69.7% of patients and less than or equal to 0.1 in the best eye in 2.3%. Factors significantly related to vision loss were age, duration of diabetes, glycated hemoglobin (HbA1c), and level of retinopathy. Mild nonproliferative retinopathy was found in 25.8% of the patients, moderate-severe nonproliferative retinopathy in 9.8% of the patients, and proliferative retinopathy in 10.6% of the patients. After adjustment for age, duration of diabetes, HbA1c, and albumin excretion rate, significant risk factors for moderate-severe nonproliferative retinopathy were blood pressure and triglyceride, and risk factors for proliferative retinopathy were triglyceride and fibrinogen. CONCLUSION: Vision loss is a common complication of patients with insulin-dependent diabetes, with diabetic retinopathy an important cause. Apart from poor glycemic control, several other potentially modifiable risk factors for retinopathy may be important, including elevated blood pressure, plasma triglyceride, and fibrinogen. In view of the possible barriers to the full implementation of strict glycemic control in this type of diabetes, additional strategies for the prevention and slowing of progression of retinopathy should be investigated, such as blood pressure and lipid lowering therapies.     

Progression of retinopathy after change of treatment from oral antihyperglycemic agents to insulin in patients with NIDDM

OBJECTIVE: In insulin-dependent diabetes mellitus, institution of good glycemic control has been shown to retard development of retinopathy even though temporary progression has occurred. Few data have been available from patients with non-insulin-dependent diabetes mellitus (NIDDM). To determine the impact of improved glycemic control on retinopathy in patients with NIDDM, we examined, in a case-control study, the progression of retinopathy in 94 patients who changed treatment from oral antihyperglycemic agents to insulin. RESEARCH DESIGN AND METHODS: We used the Wisconsin retinopathy scale and related progression of retinopathy during a 2-year observation period to changes in HbA1c after institution of insulin therapy. RESULTS: Progression of retinopathy > or = 3 levels occurred in 23% of the patients and was significantly more common in the patient group in which HbA1c was lowered > or = 3% compared with progression in the group in which HbA1c was lowered < 3% (P = 0.0001; relative risk 3.2; 95% confidence interval 1.5-6.9). CONCLUSIONS: Improved glycemic control as achieved by insulin therapy may be associated with worsening of retinopathy in patients with NIDDM.     

Type II diabetic nephropathy: its clinical course and therapeutic implications

Type II diabetes is responsible for more end-stage renal disease in the United States than any other single condition. Until recently, the majority of research in diabetic nephropathy has focused on patients with type I diabetes despite the fact that type II nephropathy is a more prevalent condition. The notion that there are major differences between the nephropathy of these two types of diabetes is not supported by recent literature. The biggest difference appears to be related to ethnic risk. Histopathologic differences are now being described as well. Clinical interventional trials are few compared to type I diabetes; however, it seems that maneuvers that improve renal prognosis in patients with type I diabetes (blood pressure control, blood glucose control, and the use of angiotensin-converting enzyme inhibitors) apply to the type II population as well. Some of the calcium channel blockers lower proteinuria to a degree that suggests renoprotection and may further improve outcome.     

Improved glycemic control in intensively treated type 1 diabetic patients using blood glucose meters with storage capability and computer-assisted analyses

OBJECTIVE: To determine the effect on glycemic control in intensively treated type 1 diabetic patients using a blood glucose meter with storage capability and computer-assisted analyses. RESEARCH DESIGN AND METHODS: Glycemic control was assessed in 22 intensively treated adults with type 1 diabetes for 12 months while using a meter without memory, followed by 12 months while using a meter with memory. Log books were used to assist patients in managing aspects of the diabetes treatment plan during the first 12-month period, and computer-assisted analyses were used when the meter with memory was used. GHb levels were measured monthly throughout the 24 months of observation. RESULTS: The mean GHb level averaged across all patients during the period of memory meter use (6.4%) was significantly lower than that during the period of meter use without memory (6.9%) (P=0.0004). The change in GHb levels from each period-specific baseline level occurred at significantly different slopes (P=0.046) when adjusted for baseline GHb level. In addition, the downward trend in GHb level was greater in those patients who increased the frequency of testing the most (r=-0.54, P=0.01). CONCLUSIONS: Use of a meter with memory in conjunction with computer-generated analyses of stored blood glucose test results can lead to improved glycemic control when used by a group of intensively treated adult diabetic patients. Improvement in glycemic control was related to frequency of blood glucose testing.     

Importance of glucose control

The importance of glycemic control in reducing the microvascular complications of type 1 diabetes has been clearly demonstrated with a long-term prospective, randomized interventional trial. The data are not as strong with regards to type 2 diabetes. The results of several prospective studies and one interventional study, however, all report benefits of improved glycemic indices on reducing microvascular complications. The available literature evaluating the relationship between glycemic control and macrovascular disease in type 1 and type 2 diabetes demonstrates the importance of glucose control. One could make rational scientific arguments or criticize the design and interpretations of any one individual study. Yet collectively the evidence is powerful. Additionally, there have been no negative studies reported. Lowering the glycosylated hemoglobin to less than 2 percentage points above the upper limit of normal should be the first glycemic goal for most patients with diabetes. Obviously, some patients cannot obtain this degree of control for a variety of reasons. Moreover, the intensity of therapy needs to be individualized and tailored to each patient. In addition, intensive glycemic control does not necessarily mean multiple injections or insulin pumps or home glucose monitoring 10 times a day. Intensive glycemic control means that the glycohemoglobin (hemoglobin and A1C and blood glucose values are in a normal or near-normal range, no matter how simple or how complex the treatment regimen. The most controversial issue is with regards to the relationship between hyperinsulinemia and accelerated atherosclerosis. This association is not consistently found in many of the large prospective studies, and certainly there has never been a direct cause-and-effect relationship proven. Most experts in the field recommend that insulin be reserved for patients with type II diabetes when oral therapy cannot achieve near-normal glycemic control. Weight gain and hypoglycemia are adverse effects of sulfonylurea and insulin therapy. These adverse effects are dwarfed, however, by the acute and chronic complications of poorly controlled diabetes. Lastly, estimates on the economic benefits of reducing long-term microvascular and macrovascular complications in populations are staggering. Based on the available literature, all patients with diabetes should be educated and have access to an appropriate individualized treatment regimen with the goal to normalize or near-normalize glycemic control. This should be the standard of care until proven otherwise.     

Insulin resistance implications for type II diabetes mellitus and coronary heart disease

PURPOSE: To review information on the implications of insulin resistance for type II diabetes mellitus (non-insulin-dependent diabetes mellitus) and coronary heart disease, and to derive guidance from this information for the management of these conditions. DATA SOURCES: A MEDLINE search of English-language articles published between 1985 and July 1996, and review of the bibliographies of articles obtained through the MEDLINE search and textbooks. STUDY SELECTION: Primary research articles, reviews and perspectives on the epidemiology of diabetes and cardiovascular diseases and on intervention outcomes in these diseases. DATA EXTRACTION: Study design and quality were assessed, with particular attention to methods, study population size and other characteristics. Conclusions of review articles and perspectives were analyzed critically. DATA SYNTHESIS: Type II diabetes is associated with a two- to fourfold excess of coronary heart disease, compared to nondiabetic populations. In most studies, glycemia and duration of clinical diabetes were found to be only weak risk factors for coronary heart disease. Conventional coronary heart disease risk factors such as dyslipidemia and hypertension have been associated with coronary heart disease in type II diabetes subjects. Hyperinsulinemia and insulin resistance have been predictive of the development of type II diabetes and, in some studies, of coronary heart disease. CONCLUSION: Strategies to prevent the development of coronary heart disease in diabetic and possibly prediabetic subjects should emphasize a multifactorial approach, including: a) improved glycemic control; b) aggressive treatment of risk factors for coronary heart disease, including insulin resistance; c) primary prevention of NIDDM; and d) use of glucose lowering agents that improve insulin sensitivity and cardiovascular risk factors.     

Pregnancy in diabetes

For patients with preconception diabetes, the most important aspect is the need for good glycemic control pre conception to lessen the risk of congenital malformations. Careful assessment of diabetes complications is essential prepregnancy. In the absence of major complications, good glycemic control gives the pregnant diabetic patient the same chance for a healthy baby as the rest of the population. Pregnancy alters carbohydrate tolerance, and thus gestational diabetes should be screened for and, when found, treated aggressively with dietary intervention, glucose monitoring, and insulin if good glycemic control has not been attained. These patients are at greatly increased risk for diabetes in the long term.     

Assessment of perinatal pathologies in premature neonates using a syllable discrimination task

OBJECTIVE: To determine the preferred treatment of clinically localized prostate cancer. DESIGN: Cancer grade, patient age, and comorbidities are considered in a Markov model with Monte Carlo sensitivity analyses. Large and recent pooled analyses and patient-derived utilities are included. RESULTS: Principal findings suggest benefit for radical prostatectomy relative to watchful waiting for men under 70 years of age with low to moderate comorbidity. Men older than 70 with high comorbidity and disease of low to moderate grade do better with watchful waiting. CONCLUSIONS: Cohort-level sensitivity analyses suggest a quality-based treatment benefit for radical prostatectomy for younger men and treatment harm for older men. Tailored patient and clinician decisions remain necessary, especially for men older than 70 in good health but with aggressive cancers.     

Gap junction expression following UVC-induced neoplastic transformation in human hybrid cell lines

OBJECTIVE: A randomized trial with 1-year follow-up was conducted in 23 general practices to study the relationship between target values for glycemic control and well-being in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 176 patients with type 2 diabetes, aged 40-75 years, were included. General practitioners were encouraged to make decisions according to a standardized step-up regimen until the target level of glycemic control was reached. The random allocation to a strict or a less strict target level of glycemic control (fasting capillary glucose < 6.5 or < 8.5 mmol/l), change in HbA1c and fasting glucose, and initiating insulin or treatment with oral hypoglycemic agents were studied as putative determinants of scores on a type 2 diabetes symptom checklist, a profile of mood states, an affect balance scale, and general well-being. Adjustments were made for baseline scores on the outcome at issue. RESULTS: Positive affect (an odds ratio [OR] [95% CI] of 0.39 [0.19-0.83]) and perceived treatment burden (OR 0.48 [0.23-0.98]) were unfavorably altered in the group randomly allocated to stricter target levels (fasting capillary glucose < 6.5 mmol/l). Patients who had a decrease in HbA1c of 1% or more tended to have comparatively favorable mood (OR displeasure score 0.35 [0.13-0.94]) and general well-being scores at 1 year (ORs of having unfavorable scores ranged from 0.4 to 0.5, NS). CONCLUSIONS: Perceived treatment burden and positive effect are unfavorably affected by random allocation to a strict target level for glycemic control. Improved glycemic control is associated with favorable mood and possibly general well-being in type 2 diabetes.     

High-fat versus high-carbohydrate enteral formulae: effect on blood glucose, C-peptide, and ketones in patients with type 2 diabetes treated with insulin or sulfonylurea

Recently, two commercial enteral formulae for diabetic patients have been made available in Spain: a high-complex-carbohydrate, low-fat formulation (HCF) and a low-carbohydrate formulation (RCF). This study compares the effects of the two enteral nutritional formulae in patients with non-insulin-dependent diabetes mellitus (type 2 diabetes) treated with sulfonylurea or insulin. Fifty-two type 2 diabetes patients were randomly assigned to receive one of the two enteral formulae. Test enteral formula breakfast (250 cc) were consumed at approximately 0900 h after routine medications (insulin or oral agents) had been taken. Venous blood samples were obtained during fasting, before medication, and at 30 and 120 min after the start of the meal. The glycemic response of patients to the HCF was significantly greater than to RCF, but lower than in the sulfonyl type 2 diabetes treated groups. The incremental glucose response was within acceptable levels except in insulin treatment type 2 diabetes patients given HCF. Glucose, insulin, and C-peptide responses were higher in HCF than RCF groups. Two-factor analysis of variance on mean increments of blood glucose and C-peptide from basal levels to 30 min show the type of enteral nutrition as the main factor (P = 0.0010 and P = 0.0005, respectively). The RCF formula supplies 50.0% of energy as fat and 33.3% as carbohydrates, so it may be a ketogenic diet. It was found that both ketone bodies were higher after RCF than after HCF ingestion, but without statistical significance. We conclude that the partial replacement of complex digestible carbohydrates with monounsaturated fatty acids in the enteral formulae for supplementation of oral diet may improve glycemic control in patients with type 2 diabetes. The long-term effects of enteral diets high in monounsaturated fatty acids need further evaluation in patients with type 2 diabetes.