Type 1 diabetes

Type 1 diabetes is caused by an autoimmune process in which the body’s immune system attacks the insulin-producing beta-cells of the pancreas. As a result, the body produces very little or no insulin. The causes of this destructive process are not fully understood but a likely explanation is that the combination of genetic susceptibility (conferred by a large number of genes) and an environmental trigger such as a viral infection, initiate the autoimmune reaction.^3,4 The condition can develop at any age, although type 1 diabetes occurs most frequently in children and young adults. Type 1 diabetes is one of the most common chronic diseases in childhood. Type 2 diabetes is also seen in older children and is increasing in some countries as childhood overweight and obesity become more common.

People with type 1 diabetes need daily insulin injections to keep their blood glucose level within an appropriate range. Without insulin, they would not survive. However, with daily insulin treatment, regular blood glucose monitoring, education and support, they can live healthy lives and delay or prevent many of the complications associated with diabetes.

A structured self-management plan comprising insulin use, blood glucose monitoring, physical activity and a healthy diet is especially difficult to follow in early childhood and adolescence. In many countries, especially in economically disadvantaged families, access to insulin and self-care tools, including structured diabetes education, can be limited. This may lead to severe disability and early death from episodes where harmful substances known as ‘ketones’ build up in the body leading to diabetic ketoacidosis (DKA).

Living with type 1 diabetes remains a challenge for a child and the whole family, even in countries with access to multiple daily injections or an insulin pump, glucose monitoring, structured diabetes education and expert medical care. Besides the acute complications of hypoglycaemia (abnormally low blood glucose) and DKA, suboptimal metabolic control may lead to poor growth and the early onset of circulatory (or ‘vascular’) complications.

The typical symptoms of type 1 diabetes are listed in Figure 1.2. The classic clinical picture of excessive thirst (polydipsia), frequent urination (polyuria) and weight loss may, however, not be present and the diagnosis delayed or even missed entirely.

Figure 1.2

The typical symptoms of type 1 diabetes.

Even in countries with universal health coverage (UHC), diagnosis of type 1 diabetes may be delayed until the first hospital admission for DKA, sometimes with fatal results.

A recent study of DKA rates at diagnosis of type 1 diabetes in 13 high-income countries showed a pooled rate for 2006–2016 of 29.9%.⁵ Prevalence ranged from 19.5% to 43.8%, and increased over time in three countries and decreased in one. This situation has prompted campaigns to increase awareness of type 1 diabetes among parents, school teachers and healthcare professionals.⁶ The latter include advocacy of ‘on-the-spot’ blood glucose measurement in an unwell child with no obvious diagnosis. In less-resourced countries, the frequency of misdiagnosis and consequent death from DKA at onset of type 1 diabetes is not known, but is likely to be very substantial in some countries.⁷

Type 1 diabetes is diagnosed by an elevated blood glucose concentration (Figure 1.1) in the presence of some or, rarely, all of the symptoms listed in Figure 1.2. However, diagnosing the type of diabetes is sometimes difficult and additional testing may be required to distinguish between type 1 and type 2 diabetes particularly the monogenic types.

The incidence of type 1 diabetes varies around the world, with some regions having much higher incidences than others.⁸ Incidence has been increasing in the great majority of countries studied, although there is now evidence that this increase is tailing off or has ceased in some high-income countries. The reasons for this are unclear but the rapid increase over time is most likely due to environmental changes.⁹

Type 2 diabetes

Type 2 diabetes is the most common type of diabetes, accounting for over 90% of all diabetes worldwide. In type 2 diabetes, hyperglycaemia is the result, initially, of the inability of the body’s cells to respond fully to insulin, a condition termed insulin resistance. With the onset of insulin resistance, the hormone is less effective and, in due course, prompts an increase in insulin production. Over time, inadequate production of insulin can develop as a result of failure of the pancreatic beta cells to keep up with demand.

Type 2 diabetes may have symptoms similar to those of type 1 diabetes but, in general, symptoms are much less dramatic and the condition may be completely symptomless. Also, the exact time of the onset of type 2 diabetes is usually impossible to determine. As a result, there is often a long pre-diagnostic period and as many as one-third to one-half of people with type 2 diabetes in the population may be undiagnosed. If the diagnosis is delayed for a prolonged time, complications such as visual impairment, poorly-healing lower-limb ulcers, heart disease or stroke may lead to the diagnosis.^10,11

The causes of type 2 diabetes are not completely understood but there is a strong link with overweight, and obesity, increasing age, ethnicity, and family history. As with type 1 diabetes, contributors to type 2 diabetes risk are thought to include polygenic and environmental triggers.

The cornerstone of type 2 diabetes management is promoting a lifestyle that includes a healthy diet, regular physical activity, smoking cessation and maintenance of healthy body weight. As a contribution to improving the management of type 2 diabetes, in 2017 IDF issued the IDF Clinical Practice Recommendations for Managing Type 2 Diabetes in Primary Care.¹² If attempts to change lifestyle are not sufficient to control blood glucose levels, oral medication is usually initiated, with metformin as the first-line medicine.

If treatment with a single antidiabetic medication is not sufficient, a range of combination therapy options are now available (e.g. sulphonylureas, alpha glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase 4 [DPP-4] inhibitors, glucagon-like peptide 1 [GLP-1] agonists and sodium glucose co-transporter 2 inhibitors). Insulin injections may be necessary to control hyperglycaemia to recommended levels if non-insulin medications fail to achieve glycaemic control.

Beyond controlling blood glucose levels, it is critically important to manage blood pressure (BP) and blood cholesterol (LDL-c) levels and to assess control of these risk factors on a regular basis (at least annually). Regular screening for the development of early diabetic complications, such as kidney disease, retinopathy, neuropathy, peripheral artery disease and foot ulceration, will allow preventive treatments where available to prevent the development and progression of these complications. With regular check-ups and effective lifestyle management, as well as medication if required, people with type 2 diabetes can lead long and healthy lives.

Globally, the prevalence of type 2 diabetes is high and rising across all regions. This rise is driven by population ageing, economic development and increasing urbanisation, leading to more sedentary lifestyles and greater consumption of unhealthy foods linked with obesity.¹³ However, the beneficial results of early detection, more effective treatment and the resulting longer survival are also contributing to the rise in prevalence.

As previously mentioned, type 2 diabetes has also become a concern in children and young people as a result of an increasing prevalence of obesity. Unfortunately, population-based studies in this area are scarce. Furthermore, there are differences in the methodologies used and the general quality of published observations.¹⁴

Nevertheless, it is clear that type 2 diabetes is particularly prevalent in some groups such as Pima and Navajo Native Americans, Aboriginal and Torres Strait Islander people in Australia and Canadian First Nation people, as well as those of Asian and Afro-American descent. In these groups, and among American-Hispanic, Japanese and Chinese children, type 2 diabetes appears to be on the increase, whereas no increase is seen in non-Hispanic white children.^15,16

Impaired glucose tolerance and impaired fasting glucose

Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are conditions of raised blood glucose levels above the normal range and below the diabetes diagnostic threshold (see Figure 1.1). The terms ‘prediabetes’, ‘non-diabetic hyperglycaemia’,¹⁷ and ‘intermediate hyperglycaemia’¹⁸ are in use as alternatives. The importance of IGT and IFG is three-fold: first, they signify a higher risk of the future development of type 2 diabetes;^19–21 second, IGT and IFG indicate an already heightened risk of CVD;^22,23 and third, their detection opens the door to interventions that can lead to the prevention of type 2 diabetes.²⁴ However, current evidence on prevention relates to isolated IGT and combined IGT and IFG but not, as yet, to isolated IFG.²⁵

Progression from IGT and IFG to type 2 diabetes is linked to glucose levels (judged by the extent of hyperglycaemia) along with risk factors such as age and weight.²⁶ The cumulative incidence of type 2 diabetes progression five years after diagnosis of IGT or IFG is estimated to be 26% and 50%, respectively.²⁰

Diagnostic criteria for diabetes

Most guidelines use the standard diagnostic criteria proposed by IDF and the World Health Organization (WHO) in Figure 1.1. The footnote in Figure 1.1 mentions the American Diabetes Association (ADA) inclusion of HbA1c as part of the diagnostic criteria of diabetes and prediabetes. WHO supports the use of HbA1c ≥ 6.5% for diabetes diagnosis but not for intermediate hyperglycaemia, on the grounds that quality-assured HbA1c measurement is not available on a global scale.²⁷

Type 2 diabetes is the most common type of diabetes, accounting for over 90% of all diabetes worldwide

Currently, WHO and IDF recommend the use of 75-gram oral glucose tolerance test (OGTT) with measurement of both fasting and two-hour plasma glucose to detect IGT and IFG. However, there is accumulating evidence favouring use of the one-hour 75-gram OGTT, which may be a more sensitive method capable of identifying intermediate hyperglycaemia.²⁸

For type 2 diabetes, in the presence of symptoms (e.g. polyuria, polydipsia and unexplained weight loss) the diagnosis can be made based on: a random venous plasma glucose concentration ≥ 11.1 mmol/l or in the absence of symptoms by a fasting plasma glucose concentration ≥ 7.0 mmol/l (whole blood ≥ 6.1 mmol/l or HbA1c ≥ 6.5%). If elevated values are detected in asymptomatic people, repeat testing, preferably with the same test, is recommended as soon as practical on a subsequent day to confirm the diagnosis.

Hyperglycaemia in pregnancy

According to WHO and the International Federation of Gynaecology and Obstetrics (FIGO), hyperglycaemia in pregnancy (HIP) can be classified as either pre-gestational diabetes, gestational diabetes mellitus (GDM) or diabetes in pregnancy (DIP).^29,30 Pre-gestational diabetes includes women with known type 1, type 2 or rarer forms of diabetes before pregnancy. GDM may occur at anytime during the antenatal period and is not expected to persist postpartum.³¹ DIP applies to pregnant women with hyperglycaemia that were first diagnosed during pregnancy and meet WHO criteria of diabetes in the non-pregnant state. DIP is best detected during the first trimester.³² It has been estimated that most (75%–90%) cases of HIP are GDM.³³

Overt symptoms of hyperglycaemia during pregnancy are rare and may be difficult to distinguish from normal pregnancy symptoms. As a result, an OGTT is recommended for the screening for GDM for all women between the 24th and 28th week of pregnancy, but for high-risk women, screening should be conducted earlier in pregnancy.³⁴ The diagnostic criteria for GDM vary and remain controversial, complicating the comparison of research data. There has been a move towards the diagnostic criteria advocated by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)/WHO^35,36 and this has resulted in a general increase in the overall prevalence of GDM.³⁷ Typically, an OGTT is performed by measuring the plasma glucose concentration while fasting and one and two hours after ingesting 75-grams of glucose. For diagnosing GDM, the criteria currently recommended across the world are summarised in Table 1.1.

Table 1.1

Diagnostic criteria in studies used for estimating hyperglycaemia in pregnancy.

Besides those women with hyperglycaemia early in pregnancy, GDM arises in women with insufficient insulin secretory capacity to overcome the diminished action of insulin (insulin resistance) due to hormone production by the placenta as pregnancy progresses.²⁹ Risk factors for GDM include older age, overweight and obesity, previous GDM, excessive weight gain during pregnancy, a family history of diabetes, polycystic ovary syndrome, habitual smoking and a history of stillbirth or giving birth to an infant with a congenital abnormality. GDM is more common in some ethnic groups.

GDM usually exists as a transient disorder during pregnancy and resolves once the pregnancy ends. However, pregnant women with hyperglycaemia are at higher risk of developing GDM in subsequent pregnancies. In addition, the relative risk of developing type 2 diabetes is particularly high at three–six years after GDM and can occur under 40 years of age. The risks remain markedly elevated thereafter.³⁷ Considering the high risk of early onset type 2 diabetes and the fact that prior GDM increases the risk of cardiovascular disease (CVD), with or without type 2 diabetes, any lifestyle intervention should be started within three years after the pregnancy in order to achieve the maximum benefit for the prevention of diabetes.^37,38 Babies born to mothers with GDM also have a higher lifetime risk of obesity and developing type 2 diabetes.³⁹

Women with hyperglycaemia detected during pregnancy are at greater risk of adverse pregnancy outcomes. These include high blood pressure (including pre-eclampsia) and a large baby for gestational age (termed ‘macrosomia’), which can make a normal birth difficult and hazardous, with the baby more prone to fractures and nerve damage. Identification of hyperglycaemia in pregnancy, combined with good control of blood glucose during pregnancy can reduce these risks. Women of child-bearing age who are known to have diabetes prior to pregnancy should receive pre-conception advice, higher dose folic acid treatment, a medication review, intensive diabetes management and a planned approach to pregnancy.

All women who have HIP – be it GDM, previously undiagnosed DIP or existing and known diabetes – require optimal antenatal care and appropriate assistance with postnatal management. Women with hyperglycaemia during pregnancy may be able to control their blood glucose levels through a healthy diet, weight management, moderate exercise and blood glucose monitoring. Interaction with healthcare professionals is important to support their self-management and also to identify when medical (e.g. prescription of insulin and/or oral medications) or obstetric intervention is needed.

Other types of diabetes

The recently published WHO report on the classification of diabetes mellitus⁴⁰ lists a number of ‘other specific types’ of diabetes, including monogenic diabetes and what was once termed ‘secondary diabetes’.

Monogenic diabetes, as the name implies, results from a single gene rather than the contribution of multiple genes and environmental factors, as seen in type 1 and type 2 diabetes. Monogenic diabetes is much less common and represents 1.5–2% of all cases, though this may well be an underestimate as it is often misdiagnosed as either type 1 or type 2 diabetes.⁴¹

These monogenic forms present a broad spectrum, from neonatal diabetes mellitus (sometimes called ‘monogenic diabetes of infancy’), maturity onset diabetes of the young (MODY) and rare diabetes-associated syndromic diseases.⁴² Although rare, these can serve as ‘human knockout models’, providing insight into diabetes pathogenesis.⁴³

From a clinical perspective, the exact diagnosis of the monogenic forms of diabetes is important because, in some instances, therapy can be tailored to the specific genetic defect.⁴¹ Further distinction between the 14 different sub-types of MODY leads not only to differences in clinical management but different predictions of complication risk. In recent years, with the accumulation of genome-wide association studies, an increasing number of monogenic forms of diabetes are being discovered.^42–44 Thus the true prevalence of these types may be underestimated.

Diabetes can also arise as a consequence of other conditions. These other specific types of diabetes are listed below, according to the most recent WHO diabetes classification.⁴⁰

Figure 1.3Other specific types of diabetes⁴⁰

Newly diagnosed diabetes cases that are not able to be classified in any of the categories that were described in this chapter, are designated as “unclassified diabetes”.

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