Diabetes mellitus
This page contains general information about Diabetes mellitus. For more information on specific types, please visit the pages:
- Diabetes mellitus type 1
- Diabetes mellitus type 2
- Gestational diabetes
Synonyms and keywords: Diabetes; DM

# Overview
Diabetes mellitus (DM) refers to a spectrum of disorders with different metabolic changes that result in hyperglycemia as a common feature. It is caused by interaction of environmental agents in a genetically susceptible person. The metabolic disarrangement that may result in hyperglycemia will define the pathologic feature of each type of DM. Decreased insulin secretion, insulin resistance, decreased glucose utilization and increased glucose production are the main metabolic dysregulations that are known to cause hyperglycemia.
Hyperglycemia may cause secondary changes in metabolic arrangement in different systems and it can involve every organ systems. DM is the leading cause of end-stage renal disease (ESRD), non-traumatic lower extremity amputations, and adult blindness worldwide.
Accordingly, early diagnosis and treatment can result in significant decrease in mortality and morbidity. The incidence of diabetes has been increased constantly. According to WHO reports, 346 million people worldwide have diabetes and it is projected to double by 2030. It's prevalence is more in developed countries but the death occurring from DM complications is more common in developing countries.
The prevalence of diabetes type 2 is more common than type 1 diabetes. Diabetes can cause many complications. Acute complications (hypoglycemia, ketoacidosis or nonketotic hyperosmolar coma) may occur if the disease is not adequately controlled. Serious long-term complications include macrovascular (coronary heart disease, peripheral arterial disease and cerebrovascular disease), microvascular (retinopathy, neuropathy and nephropathy) and other organ involvement (gastrointestinal, genitourinary, dermatologic, infectious, cataracts, glaucoma, periodontal disease and hearing loss). The main goals of treatment are:
- Elimination of hyperglycemic symptoms
- Control of the long term complications
- Improvement of the patient's quality of life

# Classification
- Diabetes mellitus is classified into 3 types based on the pathogenic process that lead to hyperglycemia:
Diabetes mellitus type 1
Diabetes mellitus type 2
Gestational diabetes
- Diabetes mellitus type 1
- Diabetes mellitus type 2
- Gestational diabetes

# Differential diagnosis

# Complications
- Complications of diabetes mellitus may be classified as acute or chronic. Acute complications of diabetes mellitus may occur in type 1, type 2, or gestational diabetes. Chronic complications of diabetes mellitus are more likely to occur in long standing type 1 or type 2 diabetes and may be further classified as macrovascular, microvascular, or other (unspecified etiology) as follows:

## Acute complications
- They include diabetic ketoacidosis (DKA) and Hyperosmolar hyperglycemic state (HHS). DKA could be the presenting feature of type 1 diabetes and it is more common in type 1 diabetes although, it is sometimes seen in type 2 diabetic patients. HHS is mostly seen in the elderly and it is more common in type 2 diabetes.

## Chronic complications

### Macrovascular
- Coronary heart disease
- Peripheral arterial disease
- Cerebrovascular disease

### Microvascular
- Retinopathy (nonproliferative/proliferative)
- Macular edema
- Sensory and motor (mono- and polyneuropathy)
- Autonomic neuropathy
- Albuminuria and declining renal function

## Other organs
- Gastrointestinal (gastroparesis, diarrhea)
- Genitourinary (uropathy/sexual dysfunction)
- Dermatologic
- Infections
- Cataracts
- Glaucoma
- Periodontal disease
- Hearing loss
- Complications of gestational diabetes differs from type 1 and type 2 diabetes primarily due to its pregnancy-specific effects on the mother as well as its effects on the fetus.
- For more information on maternal complications of gestational diabetes click here.
- For more information on fetal complications of gestational diabetes click here.

# Diagnosis

## Diabetes mellitus type 1 and type 2
- A fasting plasma glucose (FPG) <5.6 mmol/L (100 mg/dL), a plasma glucose <140 mg/dL (11.1 mmol/L) following an oral glucose challenge and an HbA1c <5.7% are considered normal. Diagnostic criteria for DM are:
Symptoms of diabetes plus random blood glucose concentration 11.1 mmol/L (200 mg/dL) OR
Fasting plasma glucose 7.0 mmol/L (126 mg/dL) OR
Hemoglobin A1c  6.5% OR
2-hoursplasma glucose 11.1 mmol/L (200 mg/dL) during an oral glucose tolerance test
- Symptoms of diabetes plus random blood glucose concentration 11.1 mmol/L (200 mg/dL) OR
- Fasting plasma glucose 7.0 mmol/L (126 mg/dL) OR
- Hemoglobin A1c  6.5% OR
- 2-hoursplasma glucose 11.1 mmol/L (200 mg/dL) during an oral glucose tolerance test
American Diabetes Association Diabetes Diagnostic Criteria 2018 (DO NOT EDIT)
- Recommendations for HbA1c:
To avoid misdiagnosis or missed diagnosis, the A1C test should be performed using a method that is certified by the NGSP and standardized to the Diabetes Control and Complications Trial (DCCT) assay. B
Marked discordance between measured A1C and plasma glucose levels should raise the possibility of A1C assay interference due to hemoglobin variants (i.e., hemoglobinopathies) and consideration of using an assay without interference or plasma blood glucose criteria to diagnose diabetes. B
In conditions associated with increased red blood cell turnover, such as sickle cell disease, pregnancy (second and third trimesters), hemodialysis, recent blood loss or transfusion, or erythropoietin therapy, only plasma blood glucose criteria should be used to diagnose diabetes. B
- To avoid misdiagnosis or missed diagnosis, the A1C test should be performed using a method that is certified by the NGSP and standardized to the Diabetes Control and Complications Trial (DCCT) assay. B
- Marked discordance between measured A1C and plasma glucose levels should raise the possibility of A1C assay interference due to hemoglobin variants (i.e., hemoglobinopathies) and consideration of using an assay without interference or plasma blood glucose criteria to diagnose diabetes. B
- In conditions associated with increased red blood cell turnover, such as sickle cell disease, pregnancy (second and third trimesters), hemodialysis, recent blood loss or transfusion, or erythropoietin therapy, only plasma blood glucose criteria should be used to diagnose diabetes. B
Note:
:Random is defined as without regard to time since the last meal.
:Fasting is defined as no caloric intake for at least 8 hours.
:The test should be performed using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water, not recommended for routine clinical use.

### American Diabetes Association Diabetes Diagnostic Criteria 2018 (DO NOT EDIT)

## Gestational diabetes
- There are 2 strategies to confirm the GDM diagnosis.
One-step 75-g Oral glucose tolerance test (OGTT) OR
Two-step approach with a 50-g (non-fasting) screen followed by a 100-g OGTT for those who screen positive.
- One-step 75-g Oral glucose tolerance test (OGTT) OR
- Two-step approach with a 50-g (non-fasting) screen followed by a 100-g OGTT for those who screen positive.

### One Step Strategy
- Perform a 75 g glucose tolerance test in 24-28 weeks of pregnancy and read the measures 1 h and 2 hours after glucose ingestion as well as fasting glucose. The OGTT should be performed in the morning after an overnight fast of at least 8 hours. The diagnosis of GDM is made when any of the following plasma glucose values are met or exceeded:
Fasting: 92 mg/dL (5.1 mmol/L)
1 hour: 180 mg/dL (10.0 mmol/L)
2 hours: 153 mg/dL (8.5 mmol/L)
- Fasting: 92 mg/dL (5.1 mmol/L)
- 1 hour: 180 mg/dL (10.0 mmol/L)
- 2 hours: 153 mg/dL (8.5 mmol/L)

### Two Step Strategy
- In this approach, screening with a 1 hour 50-g glucose load test (GLT) followed by a 3 hours 100-g OGTT for those who screen positive.
- The diagnosis of GDM is made when at least 2 out of 4 measures of 3 hours 100-g OGTT became abnormal.
- The following table summarizes the diagnostic approach for gestational diabetes.

# Screening
- Comparing developed and developing countries shows lower rate of progression from glucose intolerance to diabetes, due to better screening in developed and high-income areas.

## Diabetes mellitus type 1
- According to the American Diabetic Association, screening for type 1 DM is not recommended.

## Diabetes mellitus type 2
- Screening is recommended for many people at various stages of life, and for those with risk factors. American Diabetes Association Recommendations for Diabetes screening include:

### Categories of Increased Risk for Diabetes (Prediabetics) Recommendations:
- Screening for prediabetes and risk for future diabetes with an informal assessment of risk factors or validated tools should be considered in asymptomatic adults. B
- Testing for prediabetes and risk for future diabetes in asymptomatic people should be considered in adults of any age who are overweight or obese (BMI >25 kg/m2 or >23 kg/m2 in Asian Americans) and who have one or more additional risk factors for diabetes. B
- For all people, testing should begin at age 45 years. B
- If tests are normal, repeat testing carried out at a minimum of 3-year intervals is reasonable. C
- To test for prediabetes, fasting plasma glucose, 2-hours plasma glucose during 75-g oral glucose tolerance test, and HbA1C are equally appropriate. B
- In prediabetic patients, identify and, if appropriate, treat other risk factors of cardiovascular disease. B
- Testing for prediabetes should be considered in children and adolescents who are overweight or obese (BMI = 85th percentile for age and sex, weight for height = 85th percentile, or weight 120% of ideal for height) and who have additional risk factors for diabetes (Table 2.5). E
- To test for type 2 diabetes, fasting plasma glucose, 2-h plasma glucose after 75-g oral glucose tolerance test, and HbA1C are equally appropriate.

## Gestational diabetes
- All pregnant women should be screened for gestational diabetes in 24-28 weeks with 50 gram glucose test. Measurements greater than 130 mg/dL are considered positive and should proceed to 100 gram glucose test for diagnosis. High risk mothers should be screened as early as the first prenatal visit. These risk factors include:
A family history of diabetes especially in first degree relatives
Maternal age >25 yrs
Certain ethnic groups (such as Native American, Hispanic-American, African-American,  South or East Asian, Pacific Islander)
Body mass index greater than 25 kg/m2
Gestational diabetes or impaired glucose tolerance test in previous pregnancies
Previous delivery of a baby >9 pounds
Personal history of  impaired glucose tolerance or impaired fasting glucose (pre-diabetes)
Glycosuria at the first prenatal visit
Certain medical conditions (such as metabolic syndrome, polycystic ovary syndrome (PCOS), current use of glucocorticoids, hypertension)
Previous history of unexplained miscarriage or stillbirth
Smoking doubles the risk of gestational diabetes
Multiple gestation
Genetic predisposition (.e.g. glucokinase mutation)
- A family history of diabetes especially in first degree relatives
- Maternal age >25 yrs
- Certain ethnic groups (such as Native American, Hispanic-American, African-American,  South or East Asian, Pacific Islander)
- Body mass index greater than 25 kg/m2
- Gestational diabetes or impaired glucose tolerance test in previous pregnancies
- Previous delivery of a baby >9 pounds
- Personal history of  impaired glucose tolerance or impaired fasting glucose (pre-diabetes)
- Glycosuria at the first prenatal visit
- Certain medical conditions (such as metabolic syndrome, polycystic ovary syndrome (PCOS), current use of glucocorticoids, hypertension)
- Previous history of unexplained miscarriage or stillbirth
- Smoking doubles the risk of gestational diabetes
- Multiple gestation
- Genetic predisposition (.e.g. glucokinase mutation)

# Prevention
- Life style modification is the mainstay of prevention of diabetes mellitus. It includes, changes in diet, weight reduction and exercise.
- The strongest evidence for diabetes prevention comes from the Diabetes Prevention Program (DPP). The DPP demonstrated that an intensive lifestyle intervention could reduce the incidence of type 2 diabetes by 58% over 3 years.
- Based on a study, life style modification can improve glucose tolerance and decrease the cardiovascular complications. Even obese diabetic patients in this study showed reduced chance of diabetes mellitus development after 2 years of life style interventions.
- Patients with a modified life style had 58% less chance to develop diabetes, compared to the control group after a 3 years study. This life style modification includes physical activity, weight loss, limiting the total dietary intake, lowering intake of saturated fat and increasing dietary fiber.
- Traditionally, life style modifications mainly focused on weight loss, which is still one of the main components. Nevertheless other factors, such as better glycemic control, careful food selection, regular physical activity and consistent visits and behavioral interventions to maintain adherence are also considered crucial in new approaches.
- Intensive interdisciplinary intervention (II) on dietary habits and physical activity was related to lower blood pressure, plasma glucose and binge eating disorder (BED) frequency, compared to 9-month traditional (TI) intervention in patients at risk for diabetes. Furthermore, both interventions were effective in lowering the frequency of depression in these people.
- Study on aspirin in diabetic patients with no previous history of cardiovascular disease showed significant reduction in serious vascular events. Nevertheless, the high risk of bleeding with aspirin use overshadows this desirable outcome.
- An intervention done on 682 patients with impaired glucose tolerance test, evaluated the effect of acarbose as a possible agent for preventing the diabetes development. Based on this study, after 3 months, patients who received acarbose showed significant conversion to normal glucose level. On the other hand, patients who received placebo, had increased conversion to diabetic states.