of type 2 diabetes in obese patients. Diabetes Care. 2004; 27(1):155–161.88 88. Chiasson JL et al. Acarbose for prevention of type 2 diabetes mellitus: the STOP‐NIDDM randomised trial. Lancet. 2002; 359(9323):2072–2077.
89 89. Group NS et al. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010; 362(16):1477–1490.
90 90. Eriksson JG et al. Long‐term beneficial effects of glipizide treatment on glucose tolerance in subjects with impaired glucose tolerance. J Intern Med. 2006; 259(6):553–560.
91 91. Kanaya AM et al. Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/progestin Replacement Study. A randomized, double‐blind, placebo‐controlled trial. Ann Intern Med. 2003; 138(1):1–9.
92 92. Margolis KL et al. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative Hormone Trial. Diabetologia. 2004; 47(7):1175–1187.
93 93. Sawicki PT and Kaiser T. Response to Chiasson et al.: Acarbose for the prevention of Type 2 diabetes, hypertension and cardiovascular disease in subjects with impaired glucose tolerance: facts and interpretations concerning the critical analysis of the STOP‐NIDDM Trial data. Diabetologia. 2004; 47(6):976–977.
94 94. Lindblad U et al. Can sulphonylurea addition to lifestyle changes help to delay diabetes development in subjects with impaired fasting glucose? The Nepi ANtidiabetes StudY (NANSY). Diabetes Obes Metab. 2011; 13(2):185–188.
95 95. Pittas AG et al. Vitamin D supplementation and prevention of type 2 diabetes. N Engl J Med. 2019; 381(6):520–530.
96 96. NAVIGATOR Study Group et al. Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010; 362(16):1463–1476.
97 97. The DREAM Trial Investigators. Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006; 355(15):1551–1562.
98 98. Carlsson LM et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med. 2012; 367(8):695–704.
99 99. Pories WJ et al. Is type II diabetes mellitus (NIDDM) a surgical disease? Ann Surg. 1992; 215(6):633–642; discussion 643.
100 100. Smith AD et al. Physical activity and incident type 2 diabetes mellitus: a systematic review and dose‐response meta‐analysis of prospective cohort studies. Diabetologia. 2016; 59(12):2527–2545.
101 101. Grontved A et al. A prospective study of weight training and risk of type 2 diabetes mellitus in men. Arch Intern Med. 2012; 172(17):1306–1312.
102 102. Salas‐Salvado J et al. Prevention of diabetes with Mediterranean diets: a subgroup analysis of a randomized trial. Ann Intern Med. 2014; 160(1):1–10.
103 103. American Diabetes Association. 3. Prevention or delay of type 2 diabetes: standards of medical care in diabetes – 2020. Diabetes Care. 2020; 43(Suppl 1):S32–S36.
104 104. Hu W et al. Association of elevated glycosylated hemoglobin A1c with hyperfiltration in a middle‐aged and elderly Chinese population with prediabetes or newly diagnosed diabetes: a cross‐sectional study. BMC Endocr Disord. 2015; 15:47.
105 105. Kannan MA et al. Prevalence of neuropathy in patients with impaired glucose tolerance using various electrophysiological tests. Neurol India. 2014; 62(6):656–661.
106 106. Wu JS et al. Epidemiological evidence of altered cardiac autonomic function in subjects with impaired glucose tolerance but not isolated impaired fasting glucose. J Clin Endocrinol Metab. 2007; 92(10):3885–3889.
107 107. Holman RR et al. Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double‐blind, placebo‐controlled trial. Lancet Diabetes Endocrinol. 2017; 5(11):877–886.
2 Early Diagnosis of Type 1 Diabetes – Useful or a Pyrrhic Victory?
Paolo Pozzilli and Silvia Pieralice
Department of Endocrinology & Diabetes, Campus Bio‐Medico University of Rome, Rome, Italy
LEARNING POINTS
Making an early diagnosis of type 1 diabetes can permit intervention with agents that could modify the course of disease.
Numerous clinical trials have attempted to change the course of disease or prevent its onset. Of these, early immune intervention holds the most promise.
Introduction
Type 1 diabetes (T1D) is one of the most widespread chronic disease occurring in children and young adults. In 2001, people with diabetes (all types included) were 177 million worldwide, in 2010 285 million, in 2019 approximately 463 million and it is predicted that some 700 million people worldwide will live with diabetes in 2045 [1].
As the prevalence of diabetes continues to rise worldwide, disease‐related morbidity and mortality are emerging as major healthcare problems. Epidemiologic data show that diabetes‐related long‐term complications begin early in the natural history of the disease . These findings indicate that early identification and management of individuals at increased risk of T1D has the potential to reduce both the clinical onset of the disease and its related complications.
The global incidence of T1D in children and adolescents is rising with an estimated overall annual increase of approximately 3%. These recent epidemiologic trends in T1D have been shown in countries having both high and low prevalence figures, with an indication of a steeper increase in some of the low‐prevalence countries. T1D accounts for about 10% of all cases of diabetes, occurs most commonly in people of European descent and affects 2 million people in Europe and North America [1]. The lowest incidence has been found in Asia and Oceania, the highest in Europe.
As far as its pathogenesis is concerned, T1D results from the autoimmune destruction of pancreatic insulin‐secreting β‐cells. Genetic, metabolic, and environmental factors act together to precipitate the onset of the disease. The excess mortality associated with diabetes‐related complications and the increasing prevalence of the disease among the youth, emphasize the importance of novel therapeutic strategies to prevent or slow down the autoimmune process.
Pathogenesis of T1D: An Update in View of Defining Preventive Tools
There are three main categories of factors involved in the pathogenesis of T1D. These are genetic, immunological, and environmental factors (Figure 2.1).
Like other organ‐specific autoimmune diseases, T1D shows specific human leukocyte antigen (HLA) associations. The HLA complex on chromosome 6 comprises the first gene shown to be associated with the disease and it is considered to contribute to almost half of the familial basis of T1D. Two combinations of HLA haplotypes are of particular importance. They are DR4‐DQ8 and DR3‐DQ2, which are present in 90% of children with T1D [5]. A third haplotype, DR15‐DQ6, is found in less than 1% of children with T1D, compared to more than 20% of the general population, and it is considered to be protective. The genotype combining the two susceptibility haplotypes (DR4‐DQ8/DR3‐DQ2) contributes to the greatest risk of the disease
