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

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]Mehrian Jafarizade, M.D [3]

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:

1. Elimination of hyperglycemic symptoms
2. Control of the long term complications
3. 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

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 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

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
• 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^¶

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

ADA evidence-grading system for “Standards of Medical Care in Diabetes”

Level of evidence	Description
A	Clear evidence from well-conducted, generalizable randomized controlled trials that are adequately powered, including Evidence from a well-conducted multi-center trial Evidence from a meta-analysis that incorporated quality ratings in the analysis Compelling non-experimental evidence, i.e., “all or none” rule developed by the Center for Evidence-Based Medicine at the University of Oxford. Supportive evidence from well-conducted randomized controlled trials that are adequately powered, including Evidence from a well-conducted trial at one or more institutions Evidence from a meta-analysis that incorporated quality ratings in the analysis
B	Supportive evidence from well-conducted cohort studies Evidence from a well-conducted prospective cohort study or registry Evidence from a well-conducted meta-analysis of cohort studies Supportive evidence from a well-conducted case-control study
C	Supportive evidence from poorly controlled or uncontrolled studies Evidence from randomized clinical trials with one or more major or three or more minor flaws that could invalidate the results Evidence from observational studies with high potential for bias (such as case series with comparison with historical controls) Evidence from case series or case reports Conflicting evidence with the weight of evidence supporting the recommendation
D	Supportive evidence from poorly controlled or uncontrolled studies Evidence from randomized clinical trials with one or more major or three or more minor methodological flaws that could invalidate the results Evidence from observational studies with high potential for bias (such as case series with comparison with historical controls) Evidence from case series or case reports Conflicting evidence with the weight of evidence supporting the recommendation
E	Expert consensus or clinical experience

• 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

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)

Criteria for the diagnosis of diabetes
FPG ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 hours.
OR
2-h Plasma Glucose (PG) ≥200 mg/dL (11.1 mmol/L) during an OGTT. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.
OR
A1C ≥6.5% (48 mmol/mol). The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay. In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing.
OR
In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dL (11.1 mmol/L).

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 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)

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.

	Cut off (mg/dl)
	Fasting	1 Hour	2 Hours	3 Hours
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

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

ADA 2018 [DO NOT EDIT]

Criteria for testing for diabetes or prediabetes in asymptomatic adults
1. Testing should be considered in overweight or obese (BMI 25 kg/m2 or 23 kg/m2 in Asian Americans) adults who have one or more of the following risk factors: First-degree relative with diabetes High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander) History of CVD Hypertension (140/90 mmHg or on therapy for hypertension) HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL (2.82 mmol/L) Women with polycystic ovary syndrome Physical inactivity Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans)
2. Patients with prediabetes (A1C > 5.7% [39 mmol/mol], IGT, or IFG) should be tested yearly.
3. Women who were diagnosed with GDM should have lifelong testing at least every 3 years.
4. For all other patients, testing should begin at age 45 years.
5. If results are normal, testing should be repeated at a minimum of 3-year intervals, with consideration of more frequent testing depending on initial results and risk status.

• 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.

Categories of increased risk for diabetes (prediabetes)
FPG 100 mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L) (IFG)
OR
2-h PG during 75-g OGTT 140 mg/dL (7.8 mmol/L) to 199 mg/dL (11.0 mmol/L) (IGT)
OR
A1C 5.7–6.4% (39–47 mmol/mol)

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)

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.

References