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Diabetes mellitus : 

Diabetes mellitus Prof A K Khare

What is diabetes? : 

What is diabetes? Diabetes is a group of diseases characterized by high levels of blood glucose (blood sugar) Diabetes can lead to serious health problems and premature death About 24 million Americans have diabetes

Common types of diabetes: Type1 : 

Common types of diabetes: Type1 Type 1 diabetes is an auto-immune disease that develops when the body’s immune system destroys the pancreatic beta cells—beta cells make the hormone insulin that regulates blood glucose. People with type 1 diabetes must take insulin every day either by injection or pump. Type 1 diabetes accounts for 5% to 10% of all diagnosed cases of diabetes and usually affects children and young adults, although the disease can occur at any age. There is no known way to prevent type 1 diabetes.

Type2 : 

Type2 Type 2 diabetes usually begins as insulin resistance—a disorder in which cells do not use insulin properly. As the need for insulin rises, the pancreas gradually loses its ability to produce it. Insulin resistance and abnormal beta cell function may occur long before type 2 diabetes is diagnosed. Type 2 diabetes accounts for about 90% to 95% of all diagnosed cases of diabetes. Although still rare, type 2 diabetes is being diagnosed more frequently in children and adolescents.

GDM : 

GDM Gestational Diabetes occurs during pregnancy 5 to 10 % of women with gestational diabetes are found to have type 2 diabetes Increased lifelong risk for mother and child for developing type 2 diabetes 40-60 % women with gestational diabetes will develop diabetes in the next 5 to 10 years

Risk factors : 

Risk factors Age 45 and older Overweight (BMI ≥ 25) Hypertension Abnormal lipid levels Family history of diabetes Race/ethnicity History of gestational diabetes History of vascular disease Signs of insulin resistance (such as PCOS or acanthosis nigricans) IGT or IFG on previous test Inactive lifestyle

Cardiovascular disease and DM : 

Cardiovascular disease and DM Cardiovascular disease is the leading cause of death for people with diabetes In adults with diabetes: 68% die of heart disease or stroke the risk for stroke is two to four times higher 75% have high blood pressure smoking doubles the risk for heart disease

Diabetes complications : 

Diabetes complications Diabetes is the leading cause of: kidney failure new cases of adult blindness nontraumatic lower-limb amputations In adults with diabetes: the risk of periodontal (gum) disease is two to three times higher 60 to 70 % have mild to severe nervous system damage

DCCT : 

DCCT The Diabetes Control and Complications Trial (DCCT), an NIH-funded clinical trial, was conducted from 1983 to 1993. The DCCT is the largest, most comprehensive diabetes study ever conducted. The study compared the effects of two treatment regimens—standard therapy and intensive control—on the complications of diabetes in people with type 1 diabetes.

DCCT findings : 

DCCT findings The DCCT showed that tight glucose control slows the onset and progression of the micro vascular complications of diabetes—eye, kidney, and nerve diseases. In fact, it showed that any sustained lowering of blood glucose helps, even if the person has a history of poor control.

DCCT findings : 

DCCT findings Lowering blood glucose reduced risk of: Eye disease by 76% Kidney disease by 50% Nerve disease by 60%   DCCT. New England Journal of Medicine, 329(14), September 30, 1993.

UKPDS : 

UKPDS The United Kingdom Prospective Diabetes Study (UKPDS) was a 20 year clinical trial co-coordinated by the Diabetes Research Laboratories at Oxford. The UKPDS was designed to determine whether intensive management of type 2 diabetes in controlling blood glucose levels resulted in a reduction in long term diabetes complications compared with standard care.   Stratton IM, Et al. Association of glycemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study. BMJ. 2000; 321:405-412.

UKPDS findings : 

UKPDS findings Mirrored the findings of DCCT in people with type 2 diabetes—better glucose control reduced development of microvascular complications Demonstrated the need for management of high blood pressure and cholesterol as well as blood glucose levels (the ABCs of diabetes)

UKPDS findings : 

UKPDS findings In the UKPDS, each 1% decrease in annual mean A1C level reduced the risk of microvascular complications by 37%, peripheral vascular disease (PVD) by 43%, myocardial infarction (MI) by 14%, stroke by 12%, heart failure by 16%, and cataract extraction by 19%. These data indicate that over time there is a quantifiable relationship between the risk of complications of diabetes and glycemia.

EDIC : 

EDIC Epidemiology of Diabetes Interventions and Complications Study (EDIC) Observational study DCCT participants (type 1 diabetes) Looked at risk factors for long-term complications

EDIC findings : 

EDIC findings More than a decade after the DCCT was concluded, study participants are still benefiting from their approximately 6.5 years of intense glucose control. Lasting benefits for eye, nerve, and kidney disease Intensively treated patients had less than half the number of cardiovascular (CVD) events than the conventionally treated group. Such events included heart attacks, stroke, angina, and coronary artery disease requiring angioplasty of coronary bypass surgery.

EDIC findings : 

EDIC findings

UKPDS 10 yr Follow-Up Study- metformin group : 

UKPDS 10 yr Follow-Up Study- metformin group Differences in A1C between intensive & standard glycemic control treatment groups were lost after one year Relative risk reductions at 10 yr in intensive metformin group: 21% for any diabetes end point (P=0.01) 33% myocardial infarction (P=0.005) 21% death from any cause (P=0.002)

UKPDS blood pressure reduction findings : 

UKPDS blood pressure reduction findings For blood pressure control, the differences between the tight and standard blood pressure control groups were lost within 2 years after the end of the original study. Significant relative risk reductions in tight control group were not maintained over time for any diabetes-related end point, diabetes-related death, microvascular disease, and stroke. These finding indicate that benefits of blood pressure control do not extend beyond the period of intensified therapy. Blood pressure control must be continued if benefits are going to be maintained.

Recent trials : 

Recent trials A proven benefit of intensive glucose control: Lowers risk of new or worsening microvascular complications (damage to small vessels that cause kidney and eye damage) (ADVANCE). However, results of three major clinical trials (ADVANCE, ACCORD and VA Diabetes Trial) confirmed that intensive glucose control in type 2 diabetes presents significant risks. These are: Intensive glucose control was associated with increased mortality in patients with longstanding DM and known CVD (ACCORD). Intensive control increases risk of severe hypoglycemia (ADVANCE, ACCORD and VADT).

Key points of recent findings : 

Key points of recent findings Intensive glucose control in newly diagnosed type 1 or type 2 diabetes has benefits during intensive therapy AND a legacy effect for later micro- and macrovascular benefits Optimal glucose management should start as early as possible & continue as long as possible While the A1C goal for the general population is <7%, treatment must be individualized.

SEARCH For Diabetes in Youth Study : 

SEARCH For Diabetes in Youth Study Observational study funded by CDC and NIH Physician-diagnosed diabetes in youth ages 0-19 Data will help researchers better understand and treat diabetes in young people

SEARCH findings : 

SEARCH findings Determine prevalence and correlates of selected CVD risk factors among youth with diabetes 21% of young people with diabetes had at least two CVD risk factors Prevalence of CVD risk factors was higher among youth aged 10-19 years and among girls