Biomedical subjects

A J Garber

Publications and source records attributed to A J Garber.

78 records · Page 5Linked to original sources

PubMedDate not supplied

Metformin: mechanisms of antihyperglycemic action, other pharmacodynamic properties, and safety perspectives.

OBJECTIVE: To characterize the mechanisms of action of metformin and describe its effects and safety profile. METHODS: Results of more than 30 years of clinical use in countries other than the United States are summarized. In addition, the pharmacologic properties of metformin are compared with those of other antihyperglycemic agents. RESULTS: Approximately 90% of all cases of diabetes are non-insulin-dependent diabetes mellitus (NIDDM)--a heterogeneous disease that involves several pathogenic factors and is associated with other coexisting conditions, such as cardiovascular disease, hypertension, and obesity. Thus, an agent that controls blood glucose levels and has favorable effects on the concomitant conditions should be considered when pharmacologic intervention is needed for the treatment of NIDDM. Metformin possesses the pharmacodynamic properties to do both. Its mechanisms of action include the reduction of hepatic glucose production and enhancement of peripheral glucose disposal, making metformin an effective antihyperglycemic agent. It also has other pharmacologic properties, independent of its glycemic effects, that offer additional clinical benefits in comparison with other pharmacologic NIDDM treatments. These benefits include stabilization or even loss of weight in patients for whom weight gain is a concern and reduction of plasma lipid levels in patients with hyperlipidemia. CONCLUSION: On the basis of 3 decades of clinical experience, metformin has been shown to be not only a well tolerated but also a highly effective antihyperglycemic agent.

Journal Article↗

PubMedDate not supplied

New advances in insulin treatment of diabetes: overcoming barriers.

OBJECTIVE: To discuss the optimal role of insulin in the treatment of patients with diabetes mellitus. METHODS: We review the complications of diabetes, highlight the attempts to improve control of plasma glucose, and summarize current recommendations for use of insulin in clinical practice. RESULTS: With the strict new guidelines for the diagnosis of diabetes issued by the American Diabetes Association in July 1997--a plasma glucose level of 126 mg/dL (7 mmol/L) rather than 140 mg/dL (7.8 mmol/L)--an additional 8 million persons will be diagnosed this year, and diabetes and its complications will be at the forefront of public health concerns. Strong evidence indicates that with reduction of plasma glucose levels and tight control of glycohemoglobin, the rate of complications can be considerably decreased. Although insulin replacement therapy is well known to be both the best and the most cost-effective way to control glucose levels in patients with type 1 diabetes, studies have no shown that those with type 2 diabetes can likewise benefit from appropriate insulin therapy. Other investigations have indicated that coronary events are as likely to occur in patients with recently discovered impaired glucose tolerance as in patients with known diabetes (at a 2-hour postprandial glucose threshold of 96 mg/dL [5.3 mmol/L]). Such finding suggest that there may be no such thing as "borderline diabetes" and give impetus to the search for improved types of insulin to treat all patients with diabetes. A recent candidate is the new insulin analogue lispro, which was developed by recombinant DNA techniques, with its design influenced by the structural analogy to another endogenous hormone, insulin-like growth factor I. Lispro is a fast-acting, rapidly dissipating insulin formulation. This profile allows lispro to be given less than 15 minutes before a meal, yet with little risk of postprandial hypoglycemia because its high mealtime peak is followed by rapid disappearance from the bloodstream. CONCLUSION: Lispro has been shown to improve postprandial control of plasma glucose and to decrease the occurrence of hypoglycemia episodes in comparison with regular insulin. Because of its stability and pharmacokinetic properties, lispro can also be used in insulin pump therapy.

Journal Article↗

PubMedDate not supplied

Diabetes and atherosclerosis: mechanisms and management.

OBJECTIVE: To discuss the association of diabetes and atherosclerosis and outline various management options. METHODS: We reviewed the findings in pertinent studies in the literature. RESULTS: Atherosclerosis accounts for virtually 80% of all diabetes-related mortality. It is also a principal reason for hospitalization of patients with diabetes. Diabetes profoundly affects the pathogenesis of atherosclerosis through various mechanisms. Established cardiovascular risk factors are more prevalent in diabetic than in nondiabetic patients. Although trials of intensive glycemic control have been somewhat disappointing for decreasing atherogenesis, the results of trials with lipid-regulating therapies have been more encouraging. CONCLUSION: Atherogenesis is a multifactorial, multi-stepped process. Although established risk factors do not entirely explain the increased risk of cardiovascular disease in patients with diabetes, they do seem to have a major role. Therefore, the management of patients with diabetes must address these contributing risk factors.

Journal Article↗

PubMedDate not supplied

Impact of transfer from animal-source insulins to biosynthetic human insulin (rDNA E coli) in patients with diabetes mellitus.

Six hundred forty-eight patients (50.5% men; 49.5% women) with diabetes mellitus on animal-source insulin therapy for at least five years were studied. In this patient population, approximately 68.7% had Type I insulin-dependent diabetes mellitus and 31.3% had Type II noninsulin-dependent diabetes mellitus, nonetheless requiring insulin therapy. Patients were voluntarily transferred from animal-source insulin to biosynthetic human insulin derived by recombinant DNA technology from genetically altered Escherichia coli [human insulin (rDNAE coli)] and were monitored regularly thereafter. At a mean interval of 14 months after transfer to human insulin (rDNAE coli), these patients had gained 0.8 kg in body weight (P less than 0.01). There was a significant decline in systolic (P less than 0.01) but not in diastolic blood pressure. Insulin requirements while on animal-source insulin averaged 47.6 +/- 22.9 U/day (mean +/- SD); this requirement was not significantly different after transfer to human insulin (rDNAE coli) (47.0 +/- 21.2 U/day). The distribution of regular and modified insulin types prescribed did not change after patients were transferred from animal-source insulin to human insulin (rDNAE coli). However, a significant increase in the number of insulin injections from 1.79 +/- 0.59 to 1.96 +/- 0.61 injections/day was observed (P less than 0.001). Fasting glucose levels declined significantly from 202 +/- 87 mg/dl on animal-source insulin to 178 +/- 66 mg/dl on human insulin (rDNAE coli) (P less than 0.001). Postprandial glucose levels (at two hours) also declined from 227 +/- 83 mg/dl to 212 +/- 80 mg/dl. Glycosylated hemoglobin (HbA1c) decreased from 9.57 +/- 2.01% while taking animal insulin to 8.97 +/- 2.00% on human insulin (rDNAE coli) (P less than 0.001) Serum cholesterol and triglyceride levels insulin (rDNAE coli). Serum high-density lipoprotein cholesterol (HDL-cholesterol) levels increased from 54.2 +/- 15.1 mg/dl on animal insulin to 57.2 +/- 15.5 mg/dl on human insulin (rDNAE coli) (P less than 0.001). These data demonstrate that transfer of patients from animal-source insulins to human insulin (rDNAE coli) was associated with: (1) an improvement in glycemic control parameters; (2) a slight increase in the number of insulin injections in some patients, but no overall alteration in insulin requirements; and (3) no adverse trends in indicators of cardiovascular risks, such as serum lipids. Indeed, overall cardiovascular risk may have declined not only as a result of improvement in glycemic control, but also owing to a reduction in systolic blood pressure and an elevation in HDL-cholesterol levels.

Animals↗

PubMedDate not supplied

Availability of soluble insulin in mixed preparations of crystalline and ultralente biosynthetic human insulin.

This study investigates potential interactions between human insulins of recombinant DNA origin, specifically ultralente and crystalline Humulin, mixed in different proportions and incubated for five minutes, one hour, or 24 hours. Using insulin mixtures tested within five minutes of preparation, a mixture of less than 50% ultralente insulin produced no reduction in soluble insulin contents, whereas preparations containing greater than 80% ultralente had significantly less soluble insulin content. When premixed insulins were incubated for 24 hours before analysis, the data obtained were similar to the results after five minutes of incubation, although mixtures containing a high proportion of ultralente insulin (greater than or equal to 80% ultralente) retained somewhat more of their regular insulin content after 24 hours of interaction than after five minutes. Studies were also performed after one hour of incubation of insulin mixtures. Soluble insulin was reduced more than at either of the other two time periods investigated. Mixtures that contained greater than or equal to 70% ultralente insulin showed a reduction of greater than or equal to 50% in regular insulin content after one hour of incubation. In intensified insulin therapy programs it is usually recommended that regular insulin be administered separately from animal-source ultralente insulin preparations. The data of the present study clearly demonstrate only minor modifications of soluble insulin activity in clinically common mixtures of human ultralente and regular insulin of recombinant DNA origin. These findings are particularly important for diabetes management protocols that emphasize near normal glycemic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemistry, Pharmaceutical↗

PubMedDate not supplied

Prevention of atherosclerosis in diabetes: emphasis on treatment for the abnormal lipoprotein metabolism of diabetes.

Atherosclerosis is the principal cause of diabetic morbidity and mortality. Diabetic dyslipidemia, obesity, and hypertension are significant contributing factors in the acceleration of the atherosclerotic process. Regardless of the type of diabetes, increased levels of very-low-density lipoprotein triglyceride, modified levels of low-density lipoprotein cholesterol, and decreased levels of high-density lipoprotein (HDL) cholesterol are the main lipoprotein abnormalities in diabetic patients. These abnormalities can be improved in part by glycemic control, but additional intervention may be needed. Diet and exercise are important elements in the management of dyslipidemia, but lipid-lowering drugs (especially fibrates and HMG-CoA reductase inhibitors) also may be necessary for the control of diabetic dyslipidemia. Based on these findings, the American Diabetes Association Consensus Panel and the revised treatment guidelines of the National Cholesterol Education Program recommend treatment of hypertriglyceridemia/low HDL cholesterol as a risk factor of coronary heart disease in diabetic and nondiabetic individuals alike. Aggressive treatment is recommended, therefore, particularly in diabetic patients and in all patients with existing vascular disease.

Arteriosclerosis↗