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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #11: Epidemiology and Risk Factors for Type 1 Diabetes Mellitus Part 5 of 5

DeFronzoCoverEstablished type 1 diabetes

Clinical onset

In industrialized countries, 20–40% of T1DM patients younger than 20 years present with diabetic ketoacidosis [118]. After adjusting for age, gender, ethnicity, diabetes type, and family history of diabetes, diabetic ketoacidosis at diagnosis was associated with lower family income, less desirable health insurance coverage, and lower parental education [3]. Younger children present with more severe symptoms at diagnosis, because children younger than 7 years old have lost on average 80% of the islets, compared to 60% in those 7–14 years old and 40% in those older than 14 years [119]. Case fatality in industrialized countries ranges between 0.4–0.9% [120]. Both diabetic ketoacidosis and onset death are largely preventable, because most of the patients have typical symptoms of polyuria, polydipsia, and weight loss 2–4 weeks prior to diagnosis. The diagnosis is straightforward in almost all cases, based on the symptoms, random blood glucose over 200mg dL−1 and/or HbA1c >7%.

Traditionally, nearly all children with newly diagnosed T1DM were hospitalized. More recently, an increasing proportion of new-onset children have been managed on an outpatient basis, especially in urban centers with specialized diabetes education and treatment facilities. Hospitalization at onset does not improve short-term outcomes such as re-admission for diabetic ketoacidosis or severe hypoglycemia [118], if adequate family education and follow-up is available on outpatient basis.

Remission (honeymoon period)

Shortly after clinical onset, most T1DM patients experience a transient fall in insulin requirement due to improved β-cell function. Total and partial remissions have been reported in, respectively, 2–12% and 18–62% of young T1DM patients [118]. Older age and less severe initial presentation of T1DM and low or absent ICA or IA-2 [121] have been consistently associated with deeper and longer remission. Evidence relating GAD autoantibodies [121,122], non-Caucasian origin, HLA-DR3 allele, female gender, and family history of T1DM to a less severe presentation, greater frequency of remission, and slower deterioration of insulin secretion is inconclusive. Most studies agree that preserved beta-cell function is associated with better glycemic control (lower HbA1c) and preserved α-cell glucagon response to hypoglycemia.

The natural remission is always temporary, ending with a gradual or abrupt increase in exogenous insulin requirements. Destruction of beta cells is complete within 3 years of diagnosis in most young children, especially those with the HLA-DR3/4 genotype. It is much slower and often only partial in older patients [123], 15% of whom have still some beta-cell function preserved 10 years after diagnosis.

Acute complications

Acute complications of T1DM (diabetic ketoacidosis, hypoglycemia, and infections) are described in detail in other chapters.The risk of hospital admission for acute complication is 30/100 patient-years in the first year of the disease and 20/100 patient-years in the subsequent 3 years [118]. An estimated 26% of the patients have at least one episode of severe hypoglycemia within the initial 4 years of diagnosis. The incidence of severe hypoglycemic episodes varies between 6 and 20 per 100 person-years, and increases with younger age, longer duration of diabetes, intensity of insulin treatment, lower levels of HbA1c, and in older children with presence of underinsurance and psychiatric disorders [118,124]. The incidence of ketoacidosis is about 8 per 100 person-years and increases with age in girls; the risk of ketoacidosis also increases with higher HbA1c, higher reported insulin dose, and in older children with limited access to care due to underinsurance and presence of psychiatric disorders [124]. Interestingly, most of ketoacidosis and/or hypoglycemic episodes occur among 20% of children who have recurrent events.

Morbidity and mortality

Insulin treatment dramatically prolongs survival but it does not cure diabetes. Excess mortality seems to be lowest in Scandinavia, intermediate in the US, and highest in countries where T1DM is rare, for example, Japan, probably due to a combination of the quality of care and access. On the other hand, 40% of the patients survive over 40 years and a half of these have no major complications. Several studies have shown that survival in T1DM has improved over time [125]. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study cohort has recently shown that the life expectancy for those diagnosed 1965–1980 was 15 years greater than participants diagnosed 1950–1964, a difference that persisted regardless of sex or pubertal status at diagnosis [126]. Both the Finnish Diabetic Nephropathy (FinnDiane) study and the Pittsburgh EDC study report that in the absence of renal disease and microalbuminuria, the long-term mortality risk in T1DM is not increased compared with the general population [127].
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