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Biomedical subjects

S Genuth

Publications and source records attributed to S Genuth.

At least 19 recordsLinked to original sources
PubMed1999

Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. DCCT Skin Collagen Ancillary Study Group. Diabetes Control and Complications Trial.

The relationships between long-term intensive control of glycemia and indicators of skin collagen glycation (furosine), glycoxidation (pentosidine and N(epsilon)-[carboxymethyl]-lysine [CML]), and crosslinking (acid and pepsin solubility) were examined in 216 patients with type 1 diabetes from the primary prevention and secondary intervention cohorts of the Diabetes Control and Complications Trial. By comparison with conventional treatment, 5 years of intensive treatment was associated with 30-32% lower furosine, 9% lower pentosidine, 9-13% lower CML, 24% higher acid-soluble collagen, and 50% higher pepsin-soluble collagen. All of these differences were statistically significant in the subjects of the primary prevention cohort (P < 0.006-0.001) and also of the secondary intervention cohort (P < 0.015-0.001) with the exception of CML and acid-soluble collagen. Age- and duration-adjusted collagen variables were significantly associated with the HbA1c value nearest the biopsy and with cumulative prior HbA1c values. Multiple logistic regression analyses with six nonredundant collagen parameters as independent variables and various expressions of retinopathy, nephropathy, and neuropathy outcomes as dependent variables showed that the complications were significantly associated with the full set of collagen variables. Surprisingly, the percentage of total variance (R2) in complications explained by the collagen variables ranged from 19 to 36% with the intensive treatment and from 14 to 51% with conventional treatment. These associations generally remained significant even after adjustment for HbA1c, and, most unexpectedly, in conventionally treated subjects, glycated collagen was the parameter most consistently associated with diabetic complications. Continued monitoring of these subjects may determine whether glycation products in the skin, and especially the early Amadori product (furosine), have the potential to be predictors of the future risk of developing complications, and perhaps be even better predictors than glycated hemoglobin (HbA1c).

Adolescent↗
PubMed1996

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

PURPOSE: 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. RESULTS: 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. CONCLUSIONS: 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.

Blood Glucose↗
PubMed1996

Forum One: Current recommendations about intensification of metabolic control in non-insulin-dependent diabetes mellitus.

PURPOSE: To review issues about intensive management of non-insulin-dependent diabetes mellitus (NIDDM) and to formulate recommendations for goals and general approaches to implementation of intensive management. METHOD: A panel of clinical scientists and practitioners specializing in diabetes initially used a formal nominal process to identify the points of agreement on major issues. These points were further refined in a general conference discussion. CONCLUSIONS: 1) On the basis of data from intervention trials in IDDM that prove that intensive glycemic control reduces microvascular and neuropathic complications, coupled with epidemiologic and basic scientific data that support the strong likelihood of a similar benefit in NIDDM, the goal of treatment in NIDDM should be near-normal glycemia (glycohemoglobin level no higher than 1.0% above the upper normal limit); 2) glycemic targets should be adjusted individually according to clinical factors such as increased risk for hypoglycemia, advanced age, or reduced life expectancy from comorbid conditions; 3) some degree of comprehensive and repetitive instruction about diet and exercise and the use of blood glucose self-monitoring for all patients is essential to achieve the chosen targets; 4) intensive management of hyperglycemia should be instituted early and should initially emphasize diet and exercise therapy; staged introduction of oral hypoglycemic agents and finally insulin regimens of increasing complexity are recommended as needed to achieve glycemic targets; 5) comprehensive care must also include aggressive attempts to reduce cardiovascular risk factors (particularly hypertension, smoking, dyslipidemia, and obesity) as well as prevention of nephropathy and neuropathy; 6) the complex interaction among treatment regimens for hyperglycemia, dyslipidemia, obesity, and hypertension ideally requires a team approach, using a physician, diabetes educator, nurse, dietitian, and other health professionals; health insurers should make these resources available to generalists who currently care for most diabetic patients.

Blood Glucose↗
PubMed1996

Summary and perspectives on impaired glucose tolerance.

There is much evidence to link impaired glucose tolerance (IGT) with the risk of developing non-insulin dependent diabetes mellitus (NIDDM) and of cardiovascular disease. However, it is unclear whether IGT is merely a marker or a risk factor or whether it is causally related to the development of these conditions. It is also unclear whether all individuals with IGT have an equal probability of developing NIDDM or cardiovascular disease. The exact pathogenetic relationship between IGT and these disease has important implications for preventive therapy which might be offered to such people. Patient compliance, physician motivation and supportive health-care funding will be greater if IGT is seen to be a definite stage in the development of a serious disease rather than simply a risk factor with statistically defined predictive power. As yet, there are insufficient data to justify routine therapy of subjects with IGT but further research into this condition and the development of effective preventive therapies could lead to widespread treatment.

Blood Glucose↗
PubMed1993

The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.

BACKGROUND: Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications. METHODS: A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly. RESULTS: In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia. CONCLUSIONS: Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.

Adolescent↗
PubMed1992

Review of three decades of laboratory exercises in the preclinical curriculum at the Case Western Reserve University School of Medicine.

The authors reviewed the use of preclinical curricular time for laboratory exercises at the Case Western Reserve University School of Medicine from 1955-56 to 1988-89. Total hours decreased from over 1,000 in 1960-61 to just under 300 in 1988-89. From 1955-56 to 1985-86, laboratory hours devoted to animal and human physiology declined by 92%. Although the precise reasons for these changes--which have occurred in medical schools across the country--are difficult to document, the authors view them with concern. After considering the advantages and disadvantages of preclinical laboratory exercises, they conclude that the former still outweigh the latter. The further disappearance of laboratory exercises from the curriculum should be halted by efforts to revitalize them.

Curriculum↗
PubMed1992

Management of the adult onset diabetic with sulfonylurea drug failure.

With apparent failure of SU drug therapy, the management of NIDDM patients becomes even more challenging. The following sequence of actions is recommended. 1. Situational dietary noncompliance (eg, a prolonged vacation or a recent period of family or occupational stress) should be treated first by renewed regular contacts with the dietician. 2. Occult infection, hyperthyroidism, and prescription of hyperglycemic drugs by another physician should be ruled out. 3. If true secondary failure exists, the patient should be started on insulin therapy alone and the program optimized to lower fasting plasma glucose to less than 140 mg/dL (8 mM) and subsequently postprandial glucose levels to less than 200 mg/dL (11 mM). NPH, Lente, or Ultralente insulin given only in the evening may be considered for patients with some indication of preservation of postprandial insulin release. 4. If the patient refuses to accept insulin therapy initially, a temporary switch to another second generation SU drug may be tried, primarily to convince the patient that oral drugs alone are inadequate. 5. If optimized insulin therapy fails to achieve therapeutic goals, if multiple insulin injections are not feasible, or if goals are achieved only at the expense of very large insulin doses, then combination therapy with an SU drug may be tried.

Adult↗
PubMed1990

Insulin use in NIDDM.

The effects of insulin treatment on the pathophysiology of non-insulin-dependent diabetes mellitus (NIDDM) are reviewed herein. Short-term studies indicate variable and partial reduction in excessive hepatic glucose output, decrease in insulin resistance, and enhancement of beta-cell function. These beneficial actions may be due to a decrease in secondary glucose toxicity rather than a direct attack on the primary abnormality. Insulin should be used as initial treatment of new-onset NIDDM in the presence of ketosis, significant diabetes-induced weight loss (despite residual obesity), and severe hyperglycemic symptoms. In diet-failure patients, prospective randomized studies comparing insulin to sulfonylurea treatment show approximately equal glycemic outcomes or a slight advantage to insulin. A key goal of insulin therapy is to normalize the fasting plasma glucose level. In contrast to the conventional use of morning injections of intermediate- and long-acting insulin, preliminary studies suggest potential advantages of administering the same insulins only at bedtime. Obese patients may require several hundred units of insulin daily and still not achieve satisfactory control. In some, addition of a sulfonylurea to insulin may reduce hyperglycemia, the insulin dose, or both. However, long-term benefits from such combination therapy remain to be demonstrated conclusively. Established adverse effects of insulin treatment in NIDDM are hypoglycemia, particularly in the elderly, and weight gain. Self-monitoring of blood glucose can identify patients in whom excessive weight gain is caused by subtle hypoglycemia. Whether insulin causes weight gain by direct effects on appetite or energy utilization remains controversial. A potential adverse effect of insulin has been suggested by epidemiological studies showing associations between hyperinsulinemia or insulin resistance and increased risk for coronary artery disease, stroke, and hypertension. Although potential mechanisms for an atherogenic action of insulin exist, current evidence does not prove cause and effect and does not warrant withholding insulin therapy (or compromising on dosage) when it is needed.

Diabetes Mellitus, Type 2↗
PubMed1985

Factitious diabetic instability.

Factitious diabetic instability is described in four patients. In three the predominant problem was recurrent hypoglycaemia. The fourth presented with apparent insulin resistance and episodes of ketoacidosis. The methods used to make the diagnosis are described, and the factors which contribute to this type of diabetic instability are discussed.

Adult↗