Endothelial Dysfunction in T2DM and Atherosclerosis Development Hyperglycemia-associated vascular injury, oxidative stress, inflammation and altered hemodynamic balance may initiate atherosclerosis development and formation of arterial thrombus [ ]. Conclusions The importance of research in the fields of glucose homeostasis, insulin and diabetes has not faded. Author Contributions U.
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According to the International Diabetes Federation IDF , approximately million adults between the ages of 20 to 79 years had diabetes mellitus in In this review, we provide an overview of the pathogenesis, diagnosis, clinical presentation, and principles of management of diabetes. DM is broadly classified into three types by etiology and clinical presentation, type 1 diabetes, type 2 diabetes, and gestational diabetes GDM.
Some other less common types of diabetes include monogenic diabetes and secondary diabetes. As a result, there is an absolute deficiency of insulin. A combination of genetic susceptivity and environmental factors such as viral infection, toxins, or some dietary factors have been implicated as triggers for autoimmunity. T1DM is most commonly seen in children and adolescents though it can develop at any age. In T2DM, the response to insulin is diminished, and this is defined as insulin resistance.
During this state, insulin is ineffective and is initially countered by an increase in insulin production to maintain glucose homeostasis, but over time, insulin production decreases, resulting in T2DM.
T2DM is most commonly seen in persons older than 45 years. Still, it is increasingly seen in children, adolescents, and younger adults due to rising levels of obesity, physical inactivity, and energy-dense diets. Hyperglycaemia, which is first detected during pregnancy, is classified as gestational diabetes mellitus GDM , also known as hyperglycemia in pregnancy.
Although it can occur anytime during pregnancy, GDM generally affects pregnant women during the second and third trimesters. Women with GDM and their offspring have an increased risk of developing type 2 diabetes mellitus in the future.
GDM can be complicated by hypertension, preeclampsia, and hydramnios and may also lead to increased operative interventions. The fetus can have increased weight and size macrosomia or congenital anomalies. Even after birth, such infants may have respiratory distress syndrome and subsequent childhood and adolescent obesity. Older age, obesity, excessive gestational weight gain, history of congenital anomalies in previous children, or stillbirth, or a family history of diabetes are risk factors for GDM.
A single genetic mutation in an autosomal dominant gene causes this type of diabetes. Examples of monogenic diabetes include conditions like neonatal diabetes mellitus and maturity-onset diabetes of the young MODY. MODY is a familial disorder and usually presents under the age of 25 years. Secondary diabetes is caused due to the complication of other diseases affecting the pancreas for example, pancreatitis , hormone disturbances for example, Cushing disease , or drugs for example, corticosteroids.
Diabetes is a worldwide epidemic. With changing lifestyles and increasing obesity, the prevalence of DM has increased worldwide. The global prevalence of DM was million in Of these, 7 million were undiagnosed. With an increase in age, the prevalence of DM also increases.
In T1DM, there is cellular-mediated, autoimmune destruction of pancreatic beta cells. T1DM has a strong genetic predisposition. It occurs in adulthood, often with a slower course of onset.
The rate of destruction is generally rapid in children and faster in adults. Autoantibodies against islet cells, insulin, glutamic acid decarboxylase GAD , and zinc transporter 8 Zn T8 may be detected in the serum of such patients. These antibodies wane over time and do not have sufficient diagnostic accuracy to be used routinely for diagnosis, especially after the first year. With the progressive destruction of beta cells, there is little or no secretion of insulin.
These patients are generally not obese. They are more prone to develop other autoimmune disorders such as Addison disease, Graves disease, Hashimoto thyroiditis, and celiac disease. T2DM is an insulin-resistance condition with associated beta-cell dysfunction. Initially, there is a compensatory increase in insulin secretion, which maintains glucose levels in the normal range. As the disease progresses, beta cells change, and insulin secretion is unable to maintain glucose homeostasis, producing hyperglycemia.
Most of the patients with T2DM are obese or have a higher body fat percentage, distributed predominantly in the abdominal region. This adipose tissue itself promotes insulin resistance through various inflammatory mechanisms, including increased FFA release and adipokine dysregulation. Lack of physical activity, prior GDM in those with hypertension or dyslipidemia also increases the risk of developing T2DM.
Evolving data suggest a role for adipokine dysregulation, inflammation, abnormal incretin biology with decreased incretins such as glucagon-like peptide-1 GLP-I or incretin resistance, hyperglucagonemia, increased renal glucose reabsorption, and abnormalities in gut microbiota.
Patients with diabetes mellitus most commonly present with increased thirst, increased urination, lack of energy and fatigue, bacterial and fungal infections, and delayed wound healing. Some patients can also complain of numbness or tingling in their hands or feet or with blurred vision. These patients can have modest hyperglycemia, which can proceed to severe hyperglycemia or ketoacidosis due to infection or stress.
The height, weight, and body mass index BMI of patients with diabetes mellitus should be recorded. Retinopathy needs to be excluded in such patients by an ophthalmologist. All pulses should be palpated to examine for peripheral arterial disease. Neuropathy should be ruled out by physical examination and history. Persons older than 40 years of age should be screened annually.
More frequent screening is recommended for individuals with additional risk factors for diabetes. Women diagnosed with gestational diabetes mellitus GDM should have lifelong testing at least every three years. For all other patients, testing should begin at age 45 years, and if results are normal, patients should be tested at a minimum of every 3-years. The same tests are used to both screen for and diagnose diabetes.
These tests also detect individuals with prediabetes. Diabetes can be diagnosed either by the hemoglobin A1C criteria or plasma glucose concentration fasting or 2-hour plasma glucose. A blood sample is taken after an 8 hour overnight fast. In this test, the plasma glucose level is measured before and 2 hours after the ingestion of 75 gm of glucose. It is also a standard test but is inconvenient and more costly than FPG and has major variability issues.
Patients need to consume a diet with at least g per day of carbohydrates for 3 to 5 days and not take any medications that can impact glucose tolerance, such as steroids and thiazide diuretics. This test gives an average of blood glucose over the last 2 to 3 months. Patients with a Hb A1C greater than 6. Hb A1C is a convenient, rapid, standardized test and shows less variation due to pre-analytical variables. It is not much affected by acute illness or stress. Hb A1C is costly and has many issues, as discussed below, including lower sensitivity.
It is affected by numerous conditions such as sickle cell disease, pregnancy, hemodialysis, blood loss or transfusion, or erythropoietin therapy. It has not been well validated in non-white populations. Any approach to treatment of type 2 diabetes must combine education, diet, exercise, and management of multiple risk factors. Control of hypertension and dyslipidemia is essential.
The degree of glycemic control recommended will vary depending upon age, education, and complicating risk factors. In otherwise healthy individuals, near normalization of the glycosylated hemoglobin level is recommended , and in all cases a HbA 1c level above 8. Whether such combinations will provide long term benefit remains to be determined. In just a few years in the United States, pharmacotherapy for hyperglycemia has greatly expanded, allowing many patients whose diabetes was formerly treated by insulin alone to be controlled with oral agents.
However, much remains to be learned. New therapies will continue to evolve as insight into molecular mechanisms further expand our therapeutic horizon. However, we must now actively try to diagnose all type 2 diabetic individuals at an earlier stage and begin treatment in an attempt to minimize the burden of diabetes-associated complications.
Diabetologists and endocrinologists will play an essential part in this goal. Washington DC : U. Printing Office; NIH publication 95— Endocrinal Metab Clin North Am. Google Scholar. N Engl J Med.
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