BMJ Best Practice PDF Type 2 Diabetes in Adults

Type 2 diabetes in adults Straight to the point of care Last updated: Feb 16, 2024  Table of Contents Overview 3 Summary 3 Definition...

Type 2 diabetes in adults Straight to the point of care Last updated: Feb 16, 2024  Table of Contents Overview 3 Summary 3 Definition 3 Theory 4 Epidemiology 4 Aetiology 4 Pathophysiology 5 Case history 5 Diagnosis 7 Approach 7 History and exam 10 Risk factors 12 Investigations 13 Differentials 16 Criteria 18 Screening 19 Management 20 Approach 20 Treatment algorithm overview 46 Treatment algorithm 49 Emerging 99 Primary prevention 100 Secondary prevention 101 Patient discussions 102 Follow up 104 Monitoring 104 Complications 106 Prognosis 109 Guidelines 111 Diagnostic guidelines 111 Treatment guidelines 113 Online resources 116 Evidence tables 117 References 124 Images 157 Disclaimer 160 Type 2 diabetes in adults Overview Summary Type 2 diabetes should be managed with a personalised self-management programme, with a focus on diet and lifestyle interventions. OVERVIEW Glycaemic goals and treatment choices should be individualised. Treatment strategies should focus on the improvement of cardiovascular and kidney disease outcomes, as well as glycaemic control. Initial antihyperglycaemic therapy is with metformin, although sodium-glucose co-transporter-2 (SGLT2) inhibitors or glucagon-like peptide-1 (GLP-1) agonists are increasingly used for high-risk patients because of their cardiovascular and renal benefits. Dual therapy, triple therapy, and/or insulin may be needed to achieve good glycaemic control. Blood pressure control, lipid management, smoking cessation, and glycaemic management are important measures to reduce the risk of macrovascular complications such as heart attack and stroke, and microvascular complications, such as neuropathy, nephropathy, and retinopathy. Definition Type 2 diabetes mellitus is a progressive disorder defined by deficits in insulin secretion and increased insulin resistance that lead to abnormal glucose metabolism and related metabolic derangements. Although the aetiologies of type 1 and type 2 diabetes differ dramatically, both lead to hyperglycaemic states, and both share common macrovascular (coronary heart, cerebrovascular, and peripheral vascular disease) and microvascular (retinopathy, nephropathy, and neuropathy) complications. This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Feb 16, 2024. BMJ Best Practice topics are regularly updated and the most recent version of the topics 3 can be found on bestpractice.bmj.com. Use of this content is subject to our disclaimer (. Use of this content is subject to our). © BMJ Publishing Group Ltd 2024. All rights reserved.  Type 2 diabetes in adults Theory Epidemiology Diabetes prevalence is increasing worldwide, compounded by population growth and an ageing population. In 2000, the global diabetes prevalence in adults aged 20-79 years was estimated at 4.6%, THEORY increasing to 10.5% in 2021. Prevalence has been rising more rapidly in low- and middle-income countries than in high-income countries. Between 2000 and 2019, there was a 3% increase in age-standardised mortality rates from diabetes; in lower-middle-income countries the mortality rate due to diabetes increased by 13%. Survey data of diabetes in adults does not separate type 1 and type 2 diabetes, but most cases of diabetes (around 90%) are type 2. In most countries, the incidence of diagnosed diabetes rose from the 1990s to the mid-2000s, but has been plateauing since. It is thought that this trend might be owing to public health education and preventive strategies. Data are limited in developing countries and the trend in these regions might differ. Clinical onset of type 2 diabetes is usually preceded by many years of insulin resistance and hyperinsulinaemia before elevated glucose levels are detectable. People with type 2 diabetes have a very high risk of concurrent hypertension (80% to 90%), lipid disorders (70% to 80%), and overweight or obesity (60% to 70%). Smoking prevalence among individuals with type 2 diabetes is similar to that of the general population (current smokers: 25% vs. 28%; never-smokers: 39% vs. 42%, respectively). The most common initial cardiovascular disease complications for those with diabetes is peripheral artery disease (16.2%) and heart failure (14.1%), followed by stable angina (11.9%), non-fatal myocardial infarction (11.5%), and stroke (10.3%). On average, adults with type 2 diabetes are up to twice as likely to die of stroke or myocardial infarction compared with those without diabetes, and they are more than 40 times more likely to die of macrovascular than microvascular complications of diabetes. However, data indicate that adults with type 2 diabetes who optimally manage glucose, blood pressure, lipids, smoking, and weight have a risk of major cardiovascular events that is not significantly above the risk of age and sex- matched peers without diabetes. When diabetes is diagnosed at aged 40 years, men lose an average of 5.8 years of life, and women lose an average of 6.8 years of life, highlighting the importance of primary prevention of diabetes. However, onset of diabetes at older ages has much less effect on life expectancy if acceptable glucose, blood pressure, and lipid control can be achieved and maintained. In a large systematic review and meta-analysis, age at diabetes diagnosis was found to be inversely associated with risk of all-cause mortality and macrovascular and microvascular disease. Aetiology Type 2 diabetes often presents in people with a background genetic predisposition, and is characterised by insulin resistance and relative insulin deficiency. Insulin resistance is aggravated by ageing, overweight (body mass index [BMI] 25.0 to 29.9 kg/m²), and obesity (BMI >30 kg/m²) in particular. In addition to older age, overweight/obesity and genetic predisposition, other strong risk factors for type 2 diabetes include gestational diabetes, non-diabetic hyperglycaemia, polycystic ovary syndrome, hypertension, dyslipidaemia, cardiovascular disease, and stress. Additional risk factors have also been implicated, but their association is weaker and/or less well defined, for example insomnia, depression, autism, statin use, smoking, and caffeine consumption. 4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Feb 16, 2024. BMJ Best Practice topics are regularly updated and the most recent version of the topics can be found on bestpractice.bmj.com. Use of this content is subject to our disclaimer (. Use of this content is subject to our). © BMJ Publishing Group Ltd 2024. All rights reserved. Type 2 diabetes in adults Theory Among people with pre-diabetes/diabetes and obesity, weight loss often reduces the degree of insulin resistance and may delay diabetes onset or ameliorate diabetes severity and thereby reduce risk of long-term complications. Insulin resistance affects primarily the liver, muscle, and adipocytes, and it is characterised by complex derangements in cellular receptors, intracellular glucose kinase function, and other intracellular THEORY metabolic processes. The complexity and variety of these derangements suggest that what is now classified as type 2 diabetes may be, in fact, a larger group of conditions that await future definition. Pathophysiology In type 2 diabetes, insufficient levels of insulin fail to meet the elevated demand caused by an increased insulin resistance. Adaptive changes in beta-cell mass and beta-cell function typically allow the regulation of insulin demand during insulin resistance. If functional beta-cell compensation becomes insufficient, a cycle of incomplete glucose clearance and subsequent elevated blood glucose contributes to further deterioration of beta-cell mass and function. The increased beta-cell workload results in functional exhaustion, possible dedifferentiation, and, finally, beta-cell death. Beta-cell function is estimated to be decreased by about 50% to 80% at the time of diagnosis of type 2 diabetes, and protection and recovery of beta-cell function should be a main treatment and prevention target. While insulin resistance in the muscle and liver, along with beta-cell failure, form the three core pathophysiological components of type 2 diabetes, other contributing pathophysiological factors have been implicated in the development of glucose intolerance in type 2 diabetes. Specifically fat cells (accelerated lipolysis), the gastrointestinal tract (incretin deficiency/resistance), alpha-cells (hyperglucagonaemia), the kidney (increased glucose reabsorption), and the brain (insulin resistance) also play important roles. In 2009, DeFronzo collectively called these eight factors the ‘Ominous Octet’. The precise mechanism by which the diabetic metabolic state leads to microvascular and macrovascular complications is only partly understood, but probably involves both uncontrolled blood pressure (BP) and uncontrolled glucose. Mechanisms may involve defects in aldose reductase and other metabolic pathways, and damage to tissues from accumulation of glycated end products. With respect to macrovascular complications, high BP and glucose raise risk, but so do lipid abnormalities and tobacco use. One unifying theory postulates the existence of a metabolic syndrome that includes diabetes mellitus, hypertension, dyslipidaemias, and obesity, and predisposes to coronary heart disease, stroke, and peripheral artery disease. However, this theory is not universally accepted as more clinically useful than assessing individual cardiovascular risk factors. Case history Case history #1 A 55-year-old woman with overweight presents for preventative care. She notes that her mother died from the complications of diabetes, but reports no polyuria, polydipsia, or weight loss. BP is 144/92 mmHg, fasting blood sugar 8.2 mmol/L (148 mg/dL), HbA1c 65 mmol/mol (8.1%), LDL-cholesterol 5.18 mmol/L (200 mg/dL), HDL-cholesterol 0.8 mmol/L (30 mg/dL), and triglycerides 6.53 mmol/L (252 mg/dL). This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Feb 16, 2024. BMJ Best Practice topics are regularly updated and the most recent version of the topics 5 can be found on bestpractice.bmj.com. Use of this content is subject to our disclaimer (. Use of this content is subject to our). © BMJ Publishing Group Ltd 2024. All rights reserved.  Type 2 diabetes in adults Theory Other presentations People with type 2 diabetes can also present with symptoms such as blurred vision; fatigue; erectile dysfunction; urinary tract or candidal infections; dry itchy skin; paresthaesias; increased urination, thirst, THEORY and appetite; or unexplained weight loss. 6 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Feb 16, 2024. BMJ Best Practice topics are regularly updated and the most recent version of the topics can be found on bestpractice.bmj.com. Use of this content is subject to our disclaimer (. Use of this content is subject to our). © BMJ Publishing Group Ltd 2024. All rights reserved. Type 2 diabetes in adults Diagnosis Approach Type 2 diabetes is most often diagnosed on routine screening. Strong risk factors, which also indicate the need for screening, include: older age; overweight/obesity; certain ethnic groups (including black, South Asian, or Hispanic ancestry); family history of type 2 diabetes; history of gestational diabetes; presence of non-diabetic hyperglycaemia; polycystic ovary syndrome; hypertension; dyslipidaemia; or known cardiovascular disease. Symptomatic patients may present with fatigue, polyuria, polydipsia, polyphagia, or weight loss (usually when hyperglycaemia is more severe [e.g., >16.6 mmol/L, >300 mg/dL]); blurred vision; paraesthesias; skin infections (bacterial or candidal); urinary tract infections; or acanthosis nigricans. DIAGNOSIS Acanthosis nigricans involving the axilla From the collection of Melvin Chiu, MD; used with permission The presence of symptoms may indicate more overt hyperglycaemia. This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Feb 16, 2024. BMJ Best Practice topics are regularly updated and the most recent version of the topics 7 can be found on bestpractice.bmj.com. Use of this content is subject to our disclaimer (. Use of this content is subject to our). © BMJ Publishing Group Ltd 2024. All rights reserved.  Type 2 diabetes in adults Diagnosis Diagnosis Use the World Health Organization criteria to establish a firm diagnosis of diabetes in a non-pregnant adult: Fasting plasma glucose ≥7.0 mmol/L (≥126 mg/dL), or Plasma glucose ≥11.1 mmol/L (≥200 mg/dL) 2 hours after 75 g oral glucose, or Glycosylated haemoglobin (HbA1c) ≥48 mmol/mol (≥6.5%), or In a symptomatic patient, random plasma glucose of ≥11.1 mmol/L (≥200 mg/dL). Do not diagnose diabetes in an asymptomatic person based on a single test result. A repeat confirmatory test on a subsequent day is required in asymptomatic patients. In practice, a repeat test is often required in patients with mild-to-moderate symptoms, while a patient with severe symptoms and elevated test results does not usually need a repeat test. Check urine ketones at diagnosis if the patient is symptomatic of hyperglycaemia (polyuria, polydipsia, weakness) and volume depletion (dry mucous membranes, poor skin turgor, tachycardia, hypotension, and, in severe cases, shock). Continue to monitor throughout the course of disease. If increased ketone levels are left untreated, they can lead to progressive dehydration and diabetic ketoacidosis (DKA). DKA is a severe, life-threatening complication of diabetes. More commonly seen in people with type 1 diabetes, DKA may also occur in people with type 2 diabetes, particularly: In the presence of an underlying infection or other stressors Following cardiovascular events, malignancy, antipsychotic medication, and concomitant treatment with sodium-glucose co-transporter-2 (SGLT2) inhibitors. See our topic 'Diabetic ketoacidosis'. At initial diagnosis of diabetes, it is important to determine whether immediate treatment with insulin is required (if an adult with type 2 diabetes is symptomatically hyperglycaemic, rescue therapy of insulin or a sulfonylurea should be considered). It is also important to distinguish between type 1 and type 2 diabetes, because these conditions are DIAGNOSIS treated differently. Some individuals cannot be clearly classified as having type 1 or type 2 diabetes at the time of diagnosis. Initial classification of the diabetes subtype should be based on clinical grounds. Type 1 diabetes can occur at any age but tends to be diagnosed in younger (aged 16.6 mmol/L (>300 mg/dL) and/or HbA1c >95 mmol/ mol (>11%). polyuria (uncommon) Usually in patients with fasting plasma glucose >16.6 mmol/L (>300 mg/dL) and/or HbA1c >95 mmol/ mol (>11%). As polyuria occurs when there is considerable hyperglycaemia, it is rarely seen in people with type 2 diabetes (and is a more common presentation in people with type 1 diabetes). DIAGNOSIS Other diagnostic factors candidal infections (common) Most commonly vaginal, penile, or in skin folds. skin infections (common) Cellulitis or abscesses. urinary tract infections (common) Cystitis or pyelonephritis. fatigue (common) Increased fatigability may be an early warning sign of progressive cardiovascular disease; clinicians should have a low threshold for cardiac evaluation. blurred vision (common) Due to elevated glucose. 10 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Feb 16, 2024. BMJ Best Practice topics are regularly updated and the most recent version of the topics can be found on bestpractice.bmj.com. Use of this content is subject to our disclaimer (. Use of this content is subject to our). © BMJ Publishing Group Ltd 2024. All rights reserved. Type 2 diabetes in adults Diagnosis polyphagia (uncommon) Usually in patients with fasting plasma glucose >16.6 mmol/L (>300 mg/dL) and/or HbA1c >95 mmol/ mol (>11%). unintentional weight loss (uncommon) If marked hyperglycaemia is present. paraesthesias (uncommon) May occur in the extremities as a result of neuropathy in those with prolonged undiagnosed diabetes. acanthosis nigricans (uncommon) A velvety, light brown-to-black marking, usually on the neck, under the arms, or in the groin. Can occur at any age. Most often associated with obesity. DIAGNOSIS Acanthosis nigricans involving the axilla From the collection of Melvin Chiu, MD; used with permission This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Feb 16, 2024. BMJ Best Practice topics are regularly updated and the most recent version of the topics 11 can be found on bestpractice.bmj.com. Use of this content is subject to our disclaimer (. Use of this content is subject to our). © BMJ Publishing Group Ltd 2024. All rights reserved.  Type 2 diabetes in adults Diagnosis Risk factors Strong older age Older people are at increased risk. However, the incidence of type 2 diabetes in children and adolescents is increasing. overweight/obesity Appears to be the precipitating factor leading to clinical expression of type 2 diabetes. Compared to people without obesity, those with obesity are almost six times more likely to develop type 2 diabetes. The mean body mass index (BMI) at the time of diagnosis of diabetes in several studies is around 31 kg/m², and there is a graded increase in risk of diabetes with increasing BMI. Clinical trials have shown that weight loss is associated with delayed or decreased onset of diabetes in high-risk adults. gestational diabetes The reported incidence of type 2 diabetes after gestational diabetes varies widely. A systematic review and meta-analysis of 170,000 women estimated the risk of developing type 2 diabetes after experiencing gestational diabetes was 20% at 10 years post-delivery, increasing linearly over time to 58% at 50 years post-delivery. Further, a large population-based cohort study concluded that gestational glucose intolerance, including conditions not meeting gestational diabetes criteria, confers a high risk of type 2 diabetes in young adulthood. non-diabetic hyperglycaemia Non-diabetic hyperglycaemia (sometimes termed pre-diabetes) is a major risk factor for the onset of type 2 diabetes. The global burden of non-diabetic hyperglycaemia is substantial and growing. family history of type 2 diabetes DIAGNOSIS Although the specific genetic profile that confers risk has yet to be fully elucidated, epidemiological observations leave little doubt of a substantial genetic component. non-white ancestry Prevalence of diabetes varies by ethnic group. In the UK, type 2 diabetes is more common in people of African, African-Caribbean, and South Asian family origin. South Asian and East Asian people are at increased risk of developing type 2 diabetes, probably due to an interplay of diet, lifestyle, and genetic factors. Different prevalence rates have been observed for white Americans, Hispanic Americans, and African-Americans, with people of African, Hispanic, or American-Indian ancestry at higher risk of diabetes compared with white people. polycystic ovary syndrome Elevated risk; should be periodically screened for type 2 diabetes. hypertension Often associated with type 2 diabetes. Periodic screening is recommended in people with, or being treated for, essential hypertension due to increased prevalence of diabetes. 12 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Feb 16, 2024. BMJ Best Practice topics are regularly updated and the most recent version of the topics can be found on bestpractice.bmj.com. Use of this content is subject to our disclaimer (. Use of this content is subject to our). © BMJ Publishing Group Ltd 2024. All rights reserved. Type 2 diabetes in adults Diagnosis dyslipidaemia Especially with low levels of high-density lipoprotein (HDL) and/or high levels of triglycerides: periodic diabetes screening is recommended due to the high prevalence of diabetes in people with dyslipidaemia. Statins are associated with a small increased risk of new-onset diabetes, which is higher in people with other risk factors for diabetes, and in association with high-intensity statins and older age. cardiovascular disease Periodic diabetes screening is recommended due to the high prevalence of diabetes in people with peripheral vascular and coronary artery disease. stress Stress provokes release of hormones that elevate glucose, and there is some evidence that life stress may predispose to onset of type 2 diabetes. Investigations 1st test to order Test Result fasting plasma glucose ≥7.0 mmol/L (≥126 mg/dL) Order after a minimum 8-hour fast. Bear in mind that a repeat confirmatory test is required for diagnosis in most cases, unless severe symptoms are present. HbA1c ≥48 mmol/mol (≥6.5%) Reflects degree of hyperglycaemia over the preceding 3 months. Bear in mind that a repeat confirmatory test is required for diagnosis in most cases, unless severe symptoms are present. HbA1c is also used to monitor glycaemic control. DIAGNOSIS 2-hour post-load glucose after 75 g oral glucose ≥11.1 mmol/L (≥200 mg/dL) Plasma glucose is measured 2 hours after 75 g oral glucose load. Bear in mind that a repeat confirmatory test is required for diagnosis in most cases, unless severe symptoms are present. random plasma glucose ≥11.1 mmol/L (≥200 mg/dL) Non-fasting test. Bear in mind that a repeat confirmatory test is required for diagnosis in most cases, unless the patient has severe symptoms. Used for rapid assessment of glucose status if symptoms such as polyuria, polydipsia, or weight loss are present. This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Feb 16, 2024. BMJ Best Practice topics are regularly updated and the most recent version of the topics 13 can be found on bestpractice.bmj.com. Use of this content is subject to our disclaimer (. Use of this content is subject to our). © BMJ Publishing Group Ltd 2024. All rights reserved.  Type 2 diabetes in adults Diagnosis Other tests to consider Test Result fasting lipid profile may show high LDL, low HDL, and/or high Dyslipidaemia is common in type 2 diabetes. triglycerides urine ketones positive in instances of ketoacidosis Check urine ketones at diagnosis if the patient is symptomatic of hyperglycaemia (polyuria, polydipsia, weakness) and volume depletion (dry mucous membranes, poor skin turgor, tachycardia, hypotension, and, in severe cases, shock). Continue to monitor throughout the course of disease. If increased ketone levels are left untreated, they can lead to progressive dehydration and diabetic ketoacidosis (DKA). DKA is a severe, life-threatening complication of diabetes. More commonly seen in people with type 1 diabetes, DKA may also occur in people with type 2 diabetes, particularly in the presence of an underlying infection (or other stressors) or following cardiovascular events, malignancy, antipsychotic medication, and concomitant treatment with sodium-glucose co-transporter-2 (SGLT2) inhibitors. See our topic 'Diabetic ketoacidosis'. albumin to creatinine ratio (ACR) may be increased; ACR ≥3 mg/mmol indicates Indicates nephropathy and suggests possible other microvascular clinically important damage. proteinuria Monitored yearly. May be assessed with a random urine sample. serum creatinine and estimated GFR may show renal insufficiency GFR is calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or Modification of Diet in Renal Disease (MDRD) formulas. The CKD-EPI formula is now recommended by the Kidney Disease Outcomes Quality Initiative DIAGNOSIS (KDOQI) because it removes bias at higher GFR levels, allowing for reporting across a full range. ECG may indicate prior ischaemia Baseline assessment. A normal ECG does not rule out coronary artery disease. Patients with an abnormal resting ECG may require further cardiac investigation. ankle-brachial pressure index (ABPI) ≤0.9 is abnormal A non-invasive tool to detect peripheral arterial disease (PAD), which has a high prevalence in people with diabetes. The National Institute for Health and Care Excellence in the UK recommends that ABPI should be performed in people with suspected PAD. Due to the potential for calcification of the arteries from atherosclerotic peripheral vascular disease (which falsely elevates the ankle-brachial index), toe pressure testing is often done as an adjunct to ABPI testing. A normal ABPI value is 1.0; a normal toe pressure value is 0.7. Do not exclude a diagnosis of PAD in people with diabetes based on a normal or raised ABPI. 14 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Feb 16, 2024. BMJ Best Practice topics are regularly updated and the most recent version of the topics can be found on bestpractice.bmj.com. Use of this content is subject to our disclaimer (. Use of this content is subject to our). © BMJ Publishing Group Ltd 2024. All rights reserved. Type 2 diabetes in adults Diagnosis Test Result random C-peptide normal or high Routine serum C-peptide measurement should not be used to confirm type 1 diagnosis; however, if a negative diabetes-specific autoantibody result is obtained, or if diabetes classification remains uncertain at a subsequent visit, serum C-peptide measurement could be considered. If C-peptide testing is indicated, bear in mind that it has better discriminative value the longer the test is done after initial presentation. In clinical practice, serum C-peptide testing can be paired with blood glucose. autoantibody testing negative If the patient has received an initial diagnosis of type 2 diabetes, but has persistently/significantly raised HbA1c despite oral medication or persistent osmotic symptoms/weight loss, consider testing for autoantibodies, as the patient may have type 1 diabetes and may have been wrongly diagnosed with type 2 diabetes. Diabetes-specific autoantibodies are routinely measured in adults with an initial diagnosis of type 1 diabetes, taking into account that the false negative rate of diabetes-specific autoantibody tests is lowest at the time of diagnosis and that the false negative rate can be reduced by carrying out quantitative tests for 2 different diabetes- specific autoantibodies (with at least 1 being positive). Autoantibodies to glutamic acid decarboxylase 65 (GAD), islet cell antibodies (ICA), insulin antibodies, antibodies to tyrosine phosphatase-related islet antigen-2 (IA-2 and IA-2beta), and zinc- transporter-8 antibodies (ZnT8) can help to identify individuals with immune-mediated diabetes, although these antibodies fade with time after onset of illness. liver function tests may be elevated May identify people with non-alcoholic fatty liver disease (NAFLD). The prevalence of NAFLD in people with type 2 diabetes is thought to DIAGNOSIS be 40% to 70%. This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Feb 16, 2024. BMJ Best Practice topics are regularly updated and the most recent version of the topics 15 can be found on bestpractice.bmj.com. Use of this content is subject to our disclaimer (. Use of this content is subject to our). © BMJ Publishing Group Ltd 2024. All rights reserved.  Type 2 diabetes in adults Diagnosis Differentials Condition Differentiating signs / Differentiating tests symptoms Non-diabetic People with non-diabetic NDH is defined as raised hyperglycaemia (pre- hyperglycaemia (NDH) blood glucose levels (HbA1c diabetes) often have no specific 42 to 47 mmol/mol [6.0% differentiating signs or to 6.4%]; or fasting glucose symptoms as both NDH and 5.5 to 6.9 mmol/L [99.0 to type 2 diabetes are generally 124.2 mg/dL]) that are not in asymptomatic. the diabetes range but are associated with an increased risk of developing type 2 diabetes. Diabetes mellitus, type 1 Tends to present in Urine ketones are often childhood or adolescence present in type 1 diabetes, with the highest incidence but may be positive in type observed in children aged 10 2 diabetes if there is severe to 14 years, but can occur at volume depletion. any age. Low (