If you look at the precursors for developing type 2 diabetes you may read something like the following, "In type 2 (also called adult-onset or non insulin dependent) diabetes, the body produces insulin, but not enough to properly convert food into energy. This form of diabetes usually occurs in people who are over 40, overweight, and have a history of diabetes". This was taken from current information and is not incorrect, but today ongoing investigations in metabolism, genetics, and epidemioogy continue to push back the time of onset of the earliest lesions associated with the so-called "metabolic syndrome, "syndrome X," and ultimately to type 2 diabetes. This research has at least two implications: a better understanding of the pathophysiology of this syndrome; and the development of new clinical strategies such as earlier programs for preventative interventions and targeting "at risk" populations.
How do we define this concept? Insulin resistance has been hypothesized to unify the clustering of hypertension, glucose intolerance, hyperinsulinemia, increased levels of triglyceride and decreased HDL cholesterol, and central and overall obesity. Researchers are looking at many aspects of this syndrome. In this article we will look at the early precursors of type 2 diabetes and then examine the complications of the disease and suggestions on what to be aware of when you are diagnosed, remembering that this is your disease, not your physician's.
Researchers are looking at the temporal order of measurable defects that give rise to abnormal glucose tolerance if they are reversible, the clinical parameters that can predict progression to glucose intolerance, and the changing demographics of type 2 diabetes. In terms of metabolic defects and potential reversibility, researchers have found that people who progress toward diabetes gained more weight as both fat and lean mass than Non-Progressors. Insulin sensitively declined progressively in the Progresors and virtually all the insulin insensitivity pointed to a fundamental defect in glycogen synthesis and storage rather than glucose oxidation. Fasting insulin levels increased from NGT to IGT, and then from IGT to diabetes in a stepwise and linear manner in the Progressors. This suggests that insulin secretory defect (which appears to be a prerequisite for the development of diabetes) is relative to the degree of insulin resistance, and not an absolute defect. Early data confirm findings that diminished early insulin secretion and defects in insulin action need to act together to produce diabetes. They demonstrate that there is a temporal progression of the metabolic insults from initial defects in glucose uptake, through beta cell dysfunction, to defects in suppression of endogenous glucose production (insulin resistance in the liver). They also support the idea that interventions should be developed to target "at risk" groups very early.
There are some clinically relevant parameters to predict progression of glucose intolerance. Research tools to quantify insulin resistance and scecreatory capacity are extremely sensitive, but quite impractical in clinical practice. Several researchers have presented papers on the subject. The Insulin Resistance and Atherosclerosis Study compared the power of various measured clinical parameters (body mass index (BMI), fasting glucose (FG) to that of the same measures together with those requiring OGTT or a rapid sampling IVGTT. Results indicate that significant persons who are classified as having glucose homeostasis by one parameter are normal by the other, and that there may be ethnic variability in the proportions of persons who satisfy one or the other criteria. Further more, the physiologic phenomena measured by the two tests are possibly different, since one reflects a basal fasting state, while the other reflects the response to multiple stimuli from the gastrointestinal tract. To further explain this difference, lacking a mechanic explanation, some data point to a significant impact of the gut, gut hormones and metabolism in the splenchnic bed on the propensity to diabetes and the modulation of glycemic patterns through the course of the day. From the clinical standpoint, it reinforces the view that postprandial hyperglycemia may be an independent factor in the progression to diabetic complications, and that is worth treating in a specific manner.
The epidemic of diabetes is no where more pronounced than in non-Caucasian population in developing countries, and among minority groups in the industrial world. The imputus for this is likely to be due to predisposing genes and an inimical environment (leading to less physical activity and increased caloric intake). The most alarming new development is one that we have discussed before and that is the rise in the incidence of type 2 diabetes in the pediatric population, especially in children of non-Caucasian ethnicity. To summarize: The metabolic defect that leads to type 2 diabetes undergo a temporal progression from initial defects in tissue uptake, through beat cell dysfunction, to defects in suppression of endogenous glucose production. It is essential to assess patients familiar factors for developing diabetes. FPG and OGTT results can be highly predictive and should be used as screening teats. The categories of IFG and UGT, though overlapping, are not identical. Person who fall into either category exclusively may have different metabolic phenotypes. Postprandial hyperglycemia may be an independent risk for the development of diabetic complications.
There is an epidemic of type 2 diabetes and the metabolic syndrome in young children. This is associated with a marked increase in obesity, insulin resistance, and hypertension. Predictors of complications in type 2 diabetes are very important to understand so that we can take control of our lives rather than having the disease control our organs. These complications are usually classified as microvascular (including visual loss, end-stage renal disease, lower extremity amputations, central autonomic neuropathy, gastroparesis, and painful neuropathies), and macrovascular, or cardiovascular (including fatal and non-fatal myocardial infarction, stroke, and peripheral vascular disease).
Cardiovascular disease (CVD) complications are far more common than microvascular complications and are the leading cause of death and disability in persons with type 2 diabetes. Multiple CVD risk factors are common in type 2 diabetes. Recent clinical trials have demonstrated impressive benefits of aggressive control of blood pressure, lipids, and glucose in the type 2 diabetes. Research supports the findings that there is a continuous gradient in risk for death or complications with worsening hyperglycemia, without any apparent threshold for increased risk. Similar continuous relationships have been reported in the past for both lipids and blood pressure. Screening and treatment of hypertension and hyperlipidemia, common companions to hyperglycemia, have been shown to improve outcomes in otherwise healthy persons and are wildly recommended.
Other risk factors that should be addressed include smoking and alcohol use. It has been shown that stopping smoking and moderation in alcohol use along with improved glycemic control could contribute to lower mortality rates in diabetes. Researchers have also found that microalbuminuria, as well as gross proteinuria, increased the risk for mortality, even after accounting for other known risk factors. Research in this area suggest that treatment or prevention of abnormal urinary albumin excretion should reduce mortality in diabetes. Screening for hypertension in type 2 diabetes is important because treating elevated blood pressure reduces diabetes complications and deaths especially due to cardiovascular disease. Current national recommendations in the US specify a blood pressure of 130/85 as a treatment goal for most patients with hypertension. This goal should be aggressively pursued for persons with type 2 diabetes and there is now reason to consider treating to even lower blood pressure goals for diabetics. Finally, we need to look at the physical limitations associated with diabetes. In a study of type 2 diabetic women. self-reported physical limitations included difficulty walking 1/4 mile, climbing 10 steps, lifting 10 pounds, and doing daily chores. These effects were stronger for younger women than for older women. When researchers controlled for BMI or coronary heart disease the associations between diabetes and physical impairment diminished. This suggests that the comorbilities of diabetes complications could improve physical functioning in addition to reducing risk for other complications.
To sum up: Asymptotic hyperglycemia (IGT and undiagnosed diabetes) is associated with increased all-cause and CVD mortality, independent of other associated risk factors. Hypertension, especially elevated systolic blood pressure, is strongly, continuously associated with diabetes-related mortality and complications. Research indicates that lower the blood pressure, the lower the complications or mortality rate.
Subclinical diabetic renal disease-microalbuminuria or gross proteinuria-increases the risk for cardiovascular mortality in type 2 diabetes, independent of other associated risk factors. Diabetes and its comorbid complications are associated with substantial limitations in basic physical functions needed to perform activities of daily living.
