Diabetes mellitus type 2

It is characterized by a resistance to insulin action that is initially counteracted by increasing its production. Over time, its production will eventually decrease, leading to loss of glycemic control, which will lead to serious complications in a multitude of organs. It has a worldwide prevalence of around 6% at increasingly younger ages because it is associated with lifestyle.

Type 2 diabetes is mainly the result of the appearance of a resistance to insulin activity in muscle cells, adipocytes (fat) and liver cells. These tissues present alterations in their interaction with insulin, so that they are not able to incorporate glucose into their interior, withdrawing it from the systemic circulation, thus increasing its levels in the blood. Additionally, the pancreas is not able to increase insulin production to the extent necessary in these circumstances to control blood glucose.

The exact reasons for this are unknown. The existence of a genetic-hereditary component is known, but 80% of cases of type 2 diabetes are related to risk factors related mainly, but not exclusively, to lifestyle. Factors that may increase the risk of type 2 diabetes include:

  • Being overweight or obese are major risk factors.
  • Inactivity. Physical activity allows weight control, use of glucose for energy and increases the sensitivity of cells to insulin.
  • Waist circumference. Fat storage primarily in the abdomen, rather than the hips and thighs, is indicative of increased risk.
  • Race and ethnicity. African Americans, Hispanics, Native Americans and Asians, and Pacific Islanders are more likely to develop type 2 diabetes than Caucasians.
  • Blood lipid levels. Elevated triglyceride levels and decreased levels of HDL cholesterol increase the risk of this metabolic disorder.
  • Age. The risk increases with advancing age, especially after age 45.
  • Prediabetes or above-normal glucose levels without actually being diabetes.
  • Pregnancy-related risks. Gestational diabetes or newborn weight greater than 4 kilograms.
  • Polycystic ovary syndrome.

Type 2 diabetes is mostly associated with lifestyle-related factors, while the contribution of genetic factors has been estimated at around 26%. Because it is one of the leading causes of morbidity worldwide, and there is great variability in prevalence, severity and comorbidities across the globe, in order to unify criteria and identify genetic risk factors, a large-scale multi-ethnic GWAS analysis was performed on more than 1.4 million participants with almost 230,000 cases. As a result, up to 545 risk loci associated with both the development of DM2 and the evolution of frequent vascular complications have been identified.


Traditionally this disease was associated with adults, however, due to its important relationship with lifestyle, it is now increasingly associated with children, adolescents and young adults. Symptoms often develop slowly and progressively and may go unnoticed for years until they have diabetes-related health problems. Up to 20% of people with this type of diabetes have signs of complications at the time of diagnosis. When they occur they may include the following:

  • Increased thirst and hunger.
  • Frequent urination.
  • Unintentional and unexplained weight loss.
  • Fatigue.
  • Blurred vision.
  • sores that are slow to heal
  • frequent infections
  • Numbness or tingling in the hands or feet.
  • Darkened areas of skin, usually in the armpits and neck.

When blood glucose levels are very high after advanced progression, severe dehydration can occur, which can lead to mental confusion, drowsiness and seizures, a condition called hyperosmolar hyperglycemic state.


Healthy lifestyle choices can help prevent type 2 diabetes even if there is a family history. A healthy lifestyle includes:

  • Eating healthy, high-fiber, low-fat, low-calorie foods, preferably fruits, vegetables, or whole grains.
  • Exercising regularly and avoiding long periods of inactivity by getting up and moving around for a few minutes every 30 minutes or every hour. If you want to lose weight, exercise should be more vigorous.
  • Losing and maintaining a healthy weight can slow the progression of type 2 diabetes.
  • Avoid smoking, as it increases the risk of cardiovascular disease, as well as alcohol and other substance abuse.

There are several clinical studies that show that moderate weight loss and a daily program of half an hour of physical exercise five days a week drastically reduce the risk of developing diabetes. Additionally, the risk is reduced or the development of complications in many organs of long-term hyperglycemia is delayed. Such is the case of retinopathy on the ocular retina, nephropathy due to kidney damage, neuropathy due to central nervous system involvement, or vasculopathies that lead to an increased risk of cardiovascular accidents, arteriosclerosis, or early heart disease.

The prevention of cardiovascular risk in diabetes is of particular relevance, for which it is additionally recommended to control the other cardiovascular risk factors, especially blood pressure (normal BP: 130/80 mmHg) and cholesterol (LDL<100 mg/dL, HDL>50 mg/dL and triglycerides<150 mg/dL). Similarly, ongoing assessment of blood glucose levels is recommended to confirm that they are under adequate control by determining glycosylated hemoglobin (HbA1C) which provides long-term information and fasting blood glucose (before meals 70-130 mg/dl).

Number of observed variants

13.5 million variants

Number of risk loci analyzed in the study

514 loci


Khan MAB et al. Epidemiology of Type 2 Diabetes - Global Burden of Disease and Forecasted Trends. J Epidemiol Glob Health. 2020;10(1):107-111.

Center for Disease Control and Prevention. Diabetes [March 2022]

Mayo Clinic [March 2022]

National Institute of Diabetes and Digestive and Kidney Diseases. Diabetes [March 2022]

Vujkovic M et al. Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis. Nat Genet. 2020 Jul;52(7):680-691.

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