Abnormal sex ratio—M:F 1:3
No islet autoimmunity
Ketosis or ketoacidosis common at onset
Insulin usually not necessary for survival after treatment of acute metabolic deterioration, although diabetic control may be poor and ketoacidosis can recur without insulin treatment in some individuals
Insulin resistance not characteristic
Insulin secretion present but diminished, without long-term deterioration of islet cell function
Table 4. Maturity Onset Diabetes of the Young (MODY) (6)
MODY as a proportion of all diabetes widely variable among different populations, from 0.14% in Germany to 3% in England and 4.8% in Madras, India
Multigenerational transmission in an autosomal dominant pattern; often necessary to test asymptomatic individuals to demonstrate the presence of diabetes
Rarely affects racial/ethnic groups other than Caucasians
Onset subtle, usually before 25 years of age, with insulin usually not being required for treatment
Molecular defects in 6 genes, involving over 200 different mutations (7)
Table 5. Type 2 Diabetes (8,9)
Occurs predominantly during second decade of life, mean ∼13.5 years, but also in prepubertal children, including as young as 4 years
Much greater risk in African-American, native North American, Hispanic (especially Mexican)-American, Asian, and South Asian (Indian Peninsula) than in Caucasian individuals
Not associated with HLA specificities
75% or more have first- or second-degree relative affected
Polygenic inheritance
Variable sex ratio (M:F) from 1:4–6 in native North Americans to 1:1.7 in African-Americans, 1:1.3 in Mexican-Americans, and 1:1 in Libyan Arabs
Not usually associated with islet cell autoimmunity
Ketosis or ketoacidosis in one-third or more of newly diagnosed patients, accounting for most of the misclassification of type 2 diabetes patients as type 1 diabetes patients
Fatal complications of severe dehydration (hyperosmolar hyperglycemic coma, hypokalemia) possible at or before diagnosis
Often detected in the asymptomatic individual as a result of testing because of risk factors or during routine school or sports examinations
Insulin resistance, with other features of the insulin resistance syndrome (hyperlipidemia, hypertension, acanthosis nigricans, ovarian hyperandrogenism)
Highly variable insulin secretion, depending on disease status and duration, from delayed, but markedly elevated, to diminished; 50% reduction in insulin secretory capacity at the time of diagnosis in adults with symptoms, and insulin dependence by 6–7 years later
Obesity, with body mass index (BMI) above 85th–95th percentile for age and sex
Table 6. Autoantibody Positive Type 2 Diabetes
ICA and GADA in adults with typical type 2 diabetes, who are referred to as having either type 1.5 or, more commonly, latent autoimmune diabetes of adults (LADA) (10,11)
United Kingdom Prospective Diabetes Study (10) found that
LADA is age related: 21% of individuals 25–34 years old (n = 157) ICA positive, 34% GADA positive, and 20% positive for both antibodies, decreasing to 4%, 7%, and 2%, respectively among those 55–65 years old (n = 1769)
antibody positive individuals are significantly less overweight than antibody negative patients
glycated hemoglobin A1c (A1C) concentrations are significantly higher in antibody positive individuals
β-cell function is significantly less in antibody positive individuals, the most dramatic difference being in the younger patients, resulting in a more rapid development of insulin dependence, usually by 3 years duration
Swedish study of all individuals 15–34 years old with newly diagnosed diabetes over a two-year period (n = 764) who were tested for ICA, GADA, and IA/2A (11) found
76% classified type 1, 14% type 2, and the rest unclassified
47% of type 2 and 59% of unclassified patients positive for one or more antibodies
antibody positive type 2 or unclassifiable patients significantly lighter, with lower C-peptide concentrations, than antibody negative patients
Comparison of clinical parameters, haplotype and antibody patterns in 57 adults with type 1 diabetes, 54 with LADA, and 190 with type 2 diabetes indicates that LADA is a slowly progressive form of type 1 diabetes, rather than a variant of type 2 diabetes (12), with
