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The case for control in diabetes mellitus
Abstract:
In all diabetic animal models studied to date, microangiopathic complications develop which can be prevented by tight control and reversed by either islet cell transplantation or transplanting the diabetic kidney into a nondiabetic environment. In humans the prevalence of these complications in secondary diabetes mellitus is similar to the prevalence in genetic diabetes. Furthermore, mesangial basement membrane thickness is normal at the onset of the disease and increases shortly thereafter. These two facts strongly suggest that the microangiopathic complications are not an independent genetic component but rather are secondary to the metabolic derangements of uncontrolled diabetes. Normal kidneys transplanted into diabetic recipients developed the vascular lesions of diabetes. Conversely, two diabetic kidneys inadvertently transplanted into nondiabetic recipients showed clearing of the vascular lesions.Most retrospective studies support the conclusion that control is associated with lessened complications. The three prospective studies published to date also support this hypothesis. Because glucose concentrations cannot be brought to normal levels by present methods, the critical question is whether a major emphasis on restoring metabolism to as nearly normal as possible will help ameliorate the microangiopathic complications in our patients. The accumulated evidence would strongly favor an affirmative answer. Two daily injections of intermediate-acting insulin supplemented with small amounts of short-acting insulin as needed is one method to approach this goal.
Insights
Diabetic microangiopathic complications are secondary to metabolic issues, not genetics. Tight glucose control and restoring normal metabolism can prevent and reverse these diabetes complications.
Area of Science:
- Nephrology
- Endocrinology
- Diabetology
Background:
- Diabetic microangiopathic complications are prevalent in both genetic and secondary diabetes mellitus.
- Mesangial basement membrane thickness increases shortly after disease onset, suggesting a secondary development.
Purpose of the Study:
- To investigate whether microangiopathic complications of diabetes are genetically determined or secondary to metabolic derangements.
- To assess the impact of metabolic control on the development and reversal of these complications.
Main Methods:
- Analysis of diabetic animal models and human cases of diabetes mellitus.
- Examination of kidney transplants between diabetic and non-diabetic recipients.
- Review of retrospective and prospective studies on diabetes control and complications.
Main Results:
- Microangiopathic complications in diabetic models are preventable with tight control and reversible with transplantation.
- Diabetic kidneys transplanted into non-diabetic recipients showed lesion clearing, while normal kidneys in diabetic recipients developed lesions.
- Evidence strongly suggests complications are secondary to uncontrolled diabetes metabolism.
Conclusions:
- Microangiopathic complications are not an independent genetic component but are secondary to metabolic derangements.
- Restoring metabolism towards normal levels is crucial for ameliorating these complications in diabetic patients.
- Current evidence favors intensive metabolic management, such as insulin therapy, to combat diabetic nephropathy.