Diabetes mellitus

Diabetes mellitus Main page
Patient Information Type 1 Type 2
Overview
Classification Diabetes mellitus type 1 Diabetes mellitus type 2 Gestational diabetes
Differential Diagnosis
Complications
Screening
Diagnosis
Prevention

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]

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 types 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), nontraumatic lower extremity amputations, and adult blindness worldwide and, early diagnosis and treatment can result in significant decrease in mortality and morbidity. The incidence of diabetes has been increasing 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 due to it is more common in developing world. 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:

1. Eliminate hyperglycemic symptoms
2. Control the long term complications
3. Improve the patient's quality of life

Classification

Diabetes mellitus is classified in to 3 types based on pathogenic process that lead to hyperglycemia.

• Diabetes mellitus type 1
• Diabetes mellitus type 2
• Gestational diabetes

Differential diagnosis

Disease	History and symptoms					Laboratory findings								Additional findings
	Polyuria	Polydipsia	Polyphagia	Weight loss	Weight gain	Serum glucose	Urinary Glucose	Urine PH	Serum Sodium	Urinary Glucose	24 hrs cortisol level	C-peptide level	Serum glucagon
Type 1 Diabetes mellitus	✔	✔	✔	✔	-	↑	↑	Normal	Normal	N/↑	Normal	↓	Normal	Auto antibodies present (Anti GAD-65 and anti insulin anti bodies)
Type 2 Diabetes mellitus	✔	✔	✔	✔	-	↑	↑	Normal	Normal	↑	Normal	Normal	↑	Acanthosis nigricans
MODY	✔	✔	✔	-	✔	↑	↑	Normal	Normal	↑	Normal	Normal	N	-
Psychogenic polydipsia	✔	✔	-	-	-	Normal	Normal	Normal	↓	Normal	Normal	Normal	Normal	-
Diabetes insipidus	✔	✔	-	-	-	Normal	Normal	Normal	↑	Normal	Normal	Normal	Normal	-
Transient hyperglycemia	-	-	-	-	-	↑	↑	Normal	Normal	↑	Normal	Normal	N/↑	In hospitalized patients especially in ICU and CCU
Steroid therapy	✔	-	-	-	✔	↑	↑	Normal	Normal	↑	↑	N/↑	N/↑	Acanthosis nigricans,
RTA 1	-	-	-	✔	-	Normal	Normal	↑	Normal	↑	Normal	Normal	Normal	Hypokalemia, nephrolithiasis
Glucagonoma	-	-	-	-	-	↑	Normal	Normal	Normal	-	Normal	Normal	↑	Necrolytic migratory erythema
Cushing syndrome	-	-	-	-	✔	↑	-	Normal	↓	N/↑	↑	Normal	Normal	Moon face, obesity, buffalo hump, easy bruisibility

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's more common in type 1 diabetes although, it's not impossible to present in type 2 diabetic patients. HHS is mostly seen in elderly and is more common in type 2 diabetes.

Chronic complications

Macrovascular

• Coronary heart disease
• Peripheral arterial disease
• Cerebrovascular disease

Microvascular

Ophthalmic

• Retinopathy (nonproliferative/proliferative)
• Macular edema

Neuropathy

• Sensory and motor (mono- and polyneuropathy)
• Autonomic neuropathy

Nephropathy

• Albuminuria and declining renal function

Other organs

• Gastrointestinal (gastroparesis, diarrhea)
• Genitourinary (uropathy/sexual dysfunction)
• Dermatologic
• Infectious
• 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.

Screening

Diabetes mellitus type 1

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

Diabetes mellitus type 2

Diabetes screening is recommended for many people at various stages of life, and for those with any of several risk factors. American Diabetes Association Recommendations for Diabetes Screening include:

• The general population should be screened every 3 years, beginning at age 45 (especially if their BMI>25kg/m2).
• Younger individuals should be screened if they have BMI>25kg/m2 and at least one of the folling risk factors
  • Sedentary life style
  • 1st degree relative with DM
  • African American, Native American, Latino, Asian American, Pacific Islander
  • Low HDL-C
  • History of gestational DM
  • Polycystic ovary syndrome
  • Vascular disease

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 woman should be screened for gestational diabetes in 24-28 weeks with 50 gram glucose test. Measures greater than 130 mg/dL are considered positive and should proceed to 100 gram glucose test for diagnosis. High risk mothers should be screen as early as first perinatal 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 kg
• Personal history of impaired glucose tolerance or impared 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)

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 to define normal glucose tolerance.
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-h plasma glucose ≥11.1 mmol/L (200 mg/dL) during an oral glucose tolerance test^¶

Note:
†:Random is defined as without regard to time since the last meal.

‡:Fasting is defined as no caloric intake for at least 8 h.

¶: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.

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 (nonfasting) 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 h after glucose ingestion as well as fasting glucose. The OGTT should be performed in the morning after an overnight fast of at least 8 h. 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 h: 180 mg/dL (10.0 mmol/L)
• 2 h: 153 mg/dL (8.5 mmol/L)

Two Step Strategy

In this approach, screening with a 1 h 50-g glucose load test (GLT) followed by a 3 h 100-g OGTT for those who screen positive.

The diagnosis of GDM is made when at least 2 out of 4 measures of 3 h 100-g OGTT became abnormal.

• The following table summarizes the diagnostic approach for gestational diabetes.

	Cut off (mg/dl)
	Fasting	1 Hour	2 Hour	3 Hour
One step test 2 hour 75 g glucose tolerance test	92	180	153	----
Two step test 1 hour 50 g screening test	----	140	----	----
3 hour 100 g test if screening test became positive Carpenter/Coustan approach	95	180	155	140
National Diabetes Data Group (NDDG) approach	105	190	165	145

Prevention

Life style modification is the main stay to prevent diabetes mellitus. It include, change 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.