Handbook of Clinical Gender Medicine

K. Schenck-Gustafsson, P. R. DeCola, D. W. Pfaff, D. S. Pisetsky

• Publisher: S. Karger
• Year: 2012
• ISBN:
  9783805599306
• Topic: Medizin
• Subtopic: Psychiatrie & geistige Gesundheit

Gender medicine is an important new field in health and disease. It is derived from top-quality research and encompasses the biological and social determinants that underlie the susceptibility to disease and its consequences. In the future, consideration of the role of gender will undoubtedly become an integral feature of all research and clinical care. Defining the role of gender in medicine requires a broad perspective on biology and diverse skills in biomedical and social sciences. When these scientific disciplines come together, a revolution in medical care is in the making. Covering twelve different areas of medicine, the practical and useful Handbook of Clinical Gender Medicine provides up-to-date information on the role of gender in the clinical presentation, diagnosis, and management of a wide range of common diseases.

Metabolic Disease

Section Editor

Sigbritt Werner, MD, PhD

Department of Endocrinology, Metabolism and Diabetes

Karolinska University Hospital Huddinge

Karolinska Institutet

Stockholm, Sweden

Metabolic Disease

Schenck-Gustafsson K, DeCola PR, Pfaff DW, Pisetsky DS (eds): Handbook of Clinical Gender Medicine.
Basel, Karger, 2012, pp 268–272

______________________

Type 1 Diabetes

Ronald C.W. Ma · Juliana C.N. Chan

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China

______________________

Abstract

Type 1 diabetes is increasing in prevalence in different parts of the world. Type 1 diabetes is unique among autoimmune diseases in not having a clear female predisposition. Gender differences are present for the pattern of complications in patients with type 1 diabetes, especially with regard to cardiovascular complications. Other important gender issues to consider include pregnancy complicating type 1 diabetes as well as psychosocial issues that may complicate management of a young patient with type 1 diabetes.

Copyright © 2012 S. Karger AG, Basel

Type 1 diabetes is a disease in which hyperglycemia occurs due to loss of pancreatic insulin secretion secondary to islet cell destruction. It has marked global variation in incidence. While the prevalence of type 1 diabetes and clinical manifestation may not seem to exhibit much gender differences, important gender issues exist relating to the pattern of complications and impact on reproductive health. Furthermore, emerging evidence regarding its epidemiology, especially with regard to developmental origins, suggest there may be a significant maternal impact on the pathogenesis of type 1 diabetes.

Epidemiology

Type 1 diabetes typically occurs in childhood, with a bimodal distribution and onset usually between the ages of 4 and 6 years, with another peak in early puberty. The incidence shows great geographical variation, with the World Health Organization (WHO) Multinational Project for Childhood Diabetes (DiaMond) reporting a 350-fold difference in incidence rates among 100 populations worldwide, with the highest incidence rates seen in some of the Scandinavian countries [1]. Although most autoimmune diseases are much more common in females, this does not appear to be the case for type 1 diabetes. Interesting, while most populations show similar incidence among boys and girls, an excess boy-to-girl ratio in incidence was seen in several countries, but the converse was not seen in any country [1]. Epidemiological studies have identified interesting patterns of transmission of type 1 diabetes from one generation to the next: fathers with type 1 diabetes are more likely to transmit their risk to their offspring compared with mothers with type 1 diabetes [2]. The mechanism underlying this altered rate of transmission is not understood at present, and may be related to underlying differences in the immune system or transmission of imprinted genes, among others.

A large number of studies have reported a global increase in incidence of type 1 diabetes, which has received relatively less attention compared to the focus on the rising epidemic of type 2 diabetes. Currently, there is an estimated 3% increase in global incidence per year [3]. This increase is particularly notable in populations of previously low incidence, and therefore has led to a reduction in the North-South discrepancy. While the factors contributing to this global increase are not entirely clear, several emerging environmental risk factors have been linked with type 1 diabetes, especially viral infections, but also other factors such as immunization, exposure to cow’s milk at an early age, reduced breast feeding, low levels of vitamin D, and various perinatal factors such as increasing maternal age, birth by Caesarian section, etc. In addition, increasing childhood obesity has also been implicated in unmasking or ‘accelerating’ the manifestation of autoimmune type 1 diabetes by accelerating β-cell apoptosis in predisposed individuals [4].

Pathophysiology

While the central defect in type 1 diabetes is immune-mediated destruction of pancreatic islet cells, recent research has characterized the pathogenesis of type 1 diabetes to include loss of immune tolerance, immune-mediated destruction, and activation of inflammatory mediators in β-cells [5]. The marked variations in incidence in different regions suggest underlying environmental factors, though this has yet to be identified. Furthermore, the emerging risk factors associated with type 1 diabetes have highlighted the possible role of developmental origins with in utero, perinatal, and postnatal factors, which together with an individual’s HLA haplotype and genetic makeup impact on the immune system and alter the risk of developing type 1 diabetes [4].

Clinical Features and Diagnosis

Children with type 1 diabetes typically present with classical symptoms of hyperglycemia with polyuria, polydipsia, and weight loss. Patients may present with acute diabetic ketoacidosis, especially among younger children. With increasing awareness, type 1 diabetic patients may not present with classical ketoacidosis, but instead overt symptoms and rapid failure with oral blood glucose-lowering drugs. Rarely, patients with a known predisposition to type 1 diabetes, such as a positive family history, are diagnosed at the early stages of the disease and are asymptomatic at the time when hyperglycemia is first noted.

A diagnosis of type 1 diabetes is based on the first demonstration of biochemical evidence of hyperglycemia, followed by differentiation from other forms of diabetes, based on the clinical presentation as well as additional laboratory tests. Islet cell autoantibodies including antibodies to glutamic acid decarboxylase, IA-2, or insulin are sometimes helpful in establishing evidence of underlying autoimmune disturbances. In a study where first-degree relatives of patients with type 1 diabetes diagnosed at 20 years or under were screened for islet cell antibodies, it was noted that islet cell antibodies and islet cell autoimmunity was more prevalent in males than females.

Complications

Children with type 1 diabetes are at increased risk of diabetic microvascular complications, namely diabetic retinopathy, diabetic neuropathy, or nephropathy, which usually present in adulthood years after initial presentation. Given the onset of type 1 diabetes in childhood, affected individuals are often faced with living with the disease for much of their lives. Compared to type 2 diabetes, microvascular complications are the predominant complications in type 1 diabetic patients, which increase with suboptimal glycemic control and disease duration.

Traditionally, cardiovascular complications are less prevalent in type 1 diabetes due to less insulin resistance and cardiovascular risk factors. However, with better survival, many type 1 diabetic patients now develop diabetic nephropathy and chronic kidney disease, which is a major predictor for cardiovascular disease, notably ischemic heart disease and cerebrovascular disease. The risk of macrovascular complications is further exacerbated by the presence of obesity and other metabolic abnormalities. With increasing obesity, including in childhood, the clinical presentation of type 1 diabetes is not uncommonly accompanied by features of insulin resistance, regardless of gender.

Significant gender differences exist for cardiovascular complications, whereby female patients with type 1 diabetes have loss of cardioprotection and different presentation for IHD. This is particularly important in female patients, given that presentation with ischemic heart disease may be different with classical symptoms of angina less often reported by patients [see chapter on type 2 diabetes by Chamnan et al., pp. 273-282].

Gender Issues in the Management of Type 1 Diabetes Mellitus

Type 1 diabetes is treated with insulin, either as regular injections or via a continuous subcutaneous insulin infusion pump. The insulin regime to be used partly depends on the age of the patient and lifestyle factors including mealtimes, meal frequency, etc. Due to the abrupt onset in childhood, children growing up with diabetes often have different psychosocial issues that may impact on their personal well-being as well as interaction with family, friends, and the workplace. For example, self-regulation measures including cognitive flexibility, attention control, goal-setting, and emotional control has been shown to be associated with treatment adherence and glycemic control in boys [6]. In addition, behavioral problems, such as factitious administration of insulin, are sometimes seen, and are more often observed in girls with type 1 diabetes compared with boys.

Pregnancy and Type 1 Diabetes

Pregnancy with type 1 diabetes presents a particularly challenging problem, whereby patients may develop fluctuant glucose control and often require intensification of insulin regime and more frequent follow-up. Of note, it has been shown that offspring of mothers with type 1 diabetes have an increased risk of type 2 diabetes and obesity later in life. This may be partly related to the exposure to hyperglycemia in utero [7], which may lead to in utero hyperinsulinemia, as well as epigenetic changes, leading to altered long-term risk (see the chapter on type 2 diabetes by Chamnan et al., pp. 273-282]).

Specific Issues Relating to Sex Hormones

Insulin is known to downregulate hepatic production of sex hormone-binding globulin (SHBG), which influences sex hormone bioavailability. Therefore, in the setting of insulin deficiency, such as that seen in type 1 diabetes, it is likely there will be disturbances of sex hormone physiology. For example, it has been noted that SHBG and total testosterone are higher in male children and young adults with diabetes (predominantly typ...