Complications as mentioned in the previous section don't usually occur until years after onset of hyperglycemia. In fact, the majority of DM2 patients may note merely unspecific symptoms or none at all. Thus, clinical presentation is of minor importance for DM2 diagnosis during the early stage of the disease. Due to the high prevalence of DM2, regular check-ups should be conducted and should comprise an evaluation of blood glucose levels, lipid profiles and blood pressure. The main finding that prompts workup of DM2 is hyperglycemia as detected during routine screens. Evaluation of the latter parameters aims at assessing cardiovascular risk factors and identifying possible comorbidities.

Nevertheless, there are some symptoms and signs that may indicate DM2:

• Lethargy
• Fatigue
• Weight loss
• Polyuria and polydipsia
• Paresthesias, pruritus
• Visual impairment
• Susceptibility to infection
• Retarded wound healing

• Weight Loss

  Very low calorie diets can produce weight loss of 11-16 kg at 12 mo with persistent weight loss of 1-2 kg at 4-6 years with a very wide variation in long term results. [ncbi.nlm.nih.gov]

  Nicky Kime, Weight loss in type 2 diabetes, Independent Nurse, 2013, 9, (2013). Nicky Kime, Weight loss in type 2 diabetes, Independent Nurse, 2013, 14, (24), (2013). [oadoi.org]

• Weight Gain

  It is possible that the study was not long enough to evaluate weight gain in relation to SSB intake in subjects with no previous weight gain. [doi.org]

  It is possible that the duration of the study was not sufficient to evaluate weight-gain in relation to SSB intake in subjects with no previous weight-gain. [ncbi.nlm.nih.gov]

• Fatigue

  Fatigue: When cells lack glucose, the body becomes tired. Fatigue can interfere with daily life when a person has type 2 diabetes. [medicalnewstoday.com]

  Patients with type 2 diabetes suffer from fatigue, increased thirst and frequent infections, in addition to irregular blood sugar levels and increased risk of cardiovascular disease. [louisbolk.org]

  Early symptoms of diabetes caused by a high blood sugar level may include: Bladder, kidney, skin, or other infections that are more frequent or heal slowly Fatigue Hunger Increased thirst Increased urination Blurred vision After many years, diabetes can [nlm.nih.gov]

• Weakness

  CONCLUSIONS: Our data suggest that chemerin is a weak predictor of T2DM. © 2015 John Wiley & Sons Ltd. [ncbi.nlm.nih.gov]

  Signs of high blood sugar Signs of low blood sugar Excessive hunger, excessive thirst, excessive urination, weight loss, weakness, infections, urinary ketones, blurred vision, cramps Shaky, confused, hunger, weak, irritable, headache, tingling, nausea [precisionnutrition.com]

  You could feel weakness or have trouble going to the bathroom. Nerve damage can make it harder for men to have an erection. High blood sugar and other problems can lead to kidney damage. Your kidneys may not work as well as they used to. [nlm.nih.gov]

• Anemia

  […] adult Lipodystrophy, partial, with Rieger anomaly, short stature, and insulinopenic diabetes mellitus Maternal diabetes postpartum (after childbirth) complication Maturity onset diabetes mellitus in young Maturity onset diabetes of youth Megaloblastic anemia [icd9data.com]

  When it comes to using the A1C to diagnose diabetes, your doctor will consider factors such as your age and whether you have anemia or another problem with your blood. 1 The A1C test is not accurate in people with anemia. [niddk.nih.gov]

  Hemoglobinopathies/Anemias Interpreting A1C levels in the presence of certain hemoglobinopathies and anemia may be problematic. [care.diabetesjournals.org]

  False A1C test results may also occur in people with other problems that affect their blood or hemoglobin such as chronic kidney disease, liver disease, or anemia. [web.archive.org]

  In addition, the A1C can be misleading in patients with certain forms of anemia and hemoglobinopathies, which may also have unique ethnic or geographic distributions. [doi.org]

• Pneumonia

  The woman suffered from Type 1 respiratory failure with pneumonia and acute respiratory distress syndrome and diabetes. The second fatality was reported from the Deenanath Mangeshkar hospital, a 51-year-old female who was admitted on April 19. [hindustantimes.com]

  These include niacin, a type of vitamin B3 certain types of diuretics, also called water pills anti-seizure drugs psychiatric drugs drugs to treat human immunodeficiency virus ( HIV ) pentamidine, a drug used to treat a type of pneumonia glucocorticoids—medicines [niddk.nih.gov]

  In the latter comparison, those with diabetes still had a significantly greater risk of severe pneumonia, release of tissue injury-related enzymes, excessive uncontrolled inflammatory responses, and hypercoagulable state associated with dysregulated glucose [medscape.com]

  Your doctor will likely also recommend the pneumonia vaccine. [mayoclinic.org]

  Infection represents the commonest precipitating cause of HHS in essentially all series and occurs in 40–60% of patients, with the most common precipitating infections being pneumonia (40–60%) and urinary tract infection (5–16%) ( 40 – 42 ). [doi.org]

• Polydipsia

  Polydipsia is also a symptom of anticholinergic poisoning. [en.wikipedia.org]

  Clinical case: A 61-year-old smoker, diagnosed with LCH 9 years ago with pulmonary and hepatic involvement, without treatment, who consulted for asthenia, unquantifiable polyuria, polydipsia and 3 kg of weight loss over a period of 2 weeks. [endocrine-abstracts.org]

  Symptoms include excessive excretion of urine (polyuria), thirst (polydipsia), constant hunger, weight loss, vision changes and fatigue. These symptoms may occur suddenly. [power2dm.eu]

  The body attempts to remove the excess glucose through urination and the most common symptoms of type 2 diabetes include the following: Polydipsia (increased thirst) Polyphagia (increased hunger) Polyuria (increased frequency of urination), especially [news-medical.net]

• Nausea

  Nausea, vomiting, diarrhea, abdominal pain, and anorexia are the most common adverse effects encountered during treatment. [ncbi.nlm.nih.gov]

  It causes confused thinking, weakness, nausea and even seizure and coma. The treatment of type 2 diabetes also can produce symptoms. [drugs.com]

  Due to its delaying effects on gastric emptying, the major side effects are GI complaints of nausea, vomiting, and diarrhea. [clevelandclinicmeded.com]

  Nausea and diarrhea are possible side effects of metformin. These side effects may go away as your body gets used to the medicine or if you take the medicine with a meal. [mayoclinic.org]

  However, some experience the following: Blurred vision Feeling tired and lethargic Frequent infections Frequent urination and increased thirst Leg cramps Mood swings Nausea Sores or cuts that are slow to heal Velvety, dark skin in the armpit and neck [docdoc.com.sg]

• Abdominal Pain

  Nausea, vomiting, diarrhea, abdominal pain, and anorexia are the most common adverse effects encountered during treatment. [ncbi.nlm.nih.gov]

  Note any other symptoms such as cough, painful urination, abdominal pain, or chest pain. [emedicinehealth.com]

  Patients diagnosed with DKA develop very high blood sugar levels, abdominal pain, fruity-smelling breath, dehydration, severe weakness, lethargy, and coma. [innerbody.com]

  Symptoms include abdominal pain, vomiting, rapid breathing, extreme lethargy, and drowsiness. Patients with ketoacidosis will also have a sweet breath odor. Left untreated, this condition can lead to coma and death. [medical-dictionary.thefreedictionary.com]

  Clinical findings Abdominal pain Weight loss Classic triad Glucose intolerance Cholelithiasis Steatorrhea Achlorhydria Diagnostics Laboratory findings: ↑ somatostatin, ↑ blood glucose levels Imaging: locate the tumor Treatment Octreotide → inhibition [amboss.com]

• Delayed Gastric Emptying

  gastric emptying, risk of postprandial hypoglycemia ): nausea, abdominal bloating, loss of appetite, early satiety Diarrhea, constipation, incontinence Treatment involves prokinetic agents (e.g. metoclopramide (1 st line), erythromycin, cisapride). [amboss.com]

  Due to its delaying effects on gastric emptying, the major side effects are GI complaints of nausea, vomiting, and diarrhea. [clevelandclinicmeded.com]

  Other Glucose-Lowering Pharmacologic Agents Pramlintide, an amylin analog, is an agent that delays gastric emptying, blunts pancreatic secretion of glucagon, and enhances satiety. [frontiersin.org]

  These include impotence, orthostatic hypotension, delayed gastric emptying, diarrhea or constipation, and asymptomatic retention of urine in the bladder. [medical-dictionary.thefreedictionary.com]

• Increased Appetite

  Prediabetes Type 1 Diabetes Type 2 Diabetes No symptoms Increased or extreme thirst Increased thirst Increased appetite Increased appetite Increased fatigue Fatigue Increased or frequent urination Increased urination, especially at night Unusual weight [heart.org]

  Share on Pinterest Some symptoms of type 2 diabetes may include fatigue, increased hunger, and increased thirst. People with type 2 diabetes do not make or use insulin correctly. [medicalnewstoday.com]

  The water loss creates intense thirst and increased urination. The increased appetite ( polyphagia ) is not as clearly understood. [medical-dictionary.thefreedictionary.com]

• Hypertension

  Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. [dx.doi.org]

  Thereby, it is put on the same footing as hypertension, atherosclerosis and hypercholesteremia. [symptoma.com]

  OBJECTIVE: To determine types and frequency of side effects of antihypertensive drugs in patients with diabetes mellitus (DM) type 2 and hypertension. [ncbi.nlm.nih.gov]

• Foot Deformity

  Microvascular Complications and Foot Care To better target those at high risk for foot complications, the Standards emphasize that all patients with insensate feet, foot deformities, or a history of foot ulcers have their feet examined at every visit. [doi.org]

  All patients with insensate feet, foot deformities, or a history of foot ulcers should have their feet examined at every visit and are candidates for specialized footwear. [2] Due to disease progression, comorbidities, and nonadherence to lifestyle or [online.epocrates.com]

  Diabetic neuropathic arthropathy ( Charcot foot ): deformation of joints and bones Tarsus and tarsometatarsal joints most commonly affected Coexisting ulcers common Acute: swelling, warmth, erythema Chronic: painless bony deformities, midfoot collapse [amboss.com]

• Sweating

  Patients should be advised that low blood sugar (glucose ≤70 mg/dL) is often accompanied by symptoms such as tachycardia, sweating, shakiness, intense hunger, or confusion, and must be dealt with promptly by ingesting 15-20 g of carbohydrate (equivalent [online.epocrates.com]

  The complications of diabetes type 2 include: heart palpitations excessive sweating slurred speech whiteness of skin confusion headache anxiety numbness in fingers, toes, and lips drowsiness More severe complications of diabetes type 2 include: diabetic [practo.com]

  Common early symptoms of low blood sugar include the following: Feeling weak Feeling dizzy Feeling hungry Trembling and feeling shaky Sweating Pounding heart Pale skin Feeling frightened or anxious Late symptoms of low blood sugar include: Feeling confused [my.clevelandclinic.org]

  The signs and symptoms of low blood glucose are easy to recognize: Rapid heartbeat Sweating Whiteness of skin Anxiety Numbness in fingers, toes, and lips Sleepiness Confusion Headaches Slurred speech Mild cases of hypoglycemia can be treated by drinking [endocrineweb.com]

• Visual Impairment

  Nevertheless, there are some symptoms and signs that may indicate DM2: Lethargy Fatigue Weight loss Polyuria and polydipsia Paresthesias, pruritus Visual impairment Susceptibility to infection Retarded wound healing Detection of hyperglycemia during routine [symptoma.com]

  Diabetologia 2001, 44 Suppl 2:S14–S21. (7) Global data on visual impairments 2010. Geneva, World Health Organization, 2012. (8) Roglic G, Unwin N, Bennett PH, Mathers C, Tuomilehto J, Nag S et al. [web.archive.org]

  The most common cause of visual impairment and blindness in patients aged 25–74 years in the US Symptoms : asymptomatic until very late stages of disease Visual impairment Progression to blindness Ophthalmological findings and classification of diabetic [amboss.com]

  Visual impairment and blindness are common sequelae of uncontrolled diabetes. [medical-dictionary.thefreedictionary.com]

  Long haul complexities from high aldohexose incorporate coronary malady, strokes, diabetic retinopathy which can bring about visual impairment, kidney disappointment, and poor blood stream in the appendages which may prompt removals. [diabetesexpo.com]

• Polyuria

  One study from 2008 lays out a hypothesis that hyperglycaemic and osmotic polyuria play roles ultimately in diabetic nephropathy.[39] Diagnosis[edit] Among the possible tests to diagnose polyuria are:[4] Treatment[edit] Depending on the cause of the polyuria [en.wikipedia.org]

  Clinical case: A 61-year-old smoker, diagnosed with LCH 9 years ago with pulmonary and hepatic involvement, without treatment, who consulted for asthenia, unquantifiable polyuria, polydipsia and 3 kg of weight loss over a period of 2 weeks. [endocrine-abstracts.org]

  Symptoms include excessive excretion of urine (polyuria), thirst (polydipsia), constant hunger, weight loss, vision changes and fatigue. These symptoms may occur suddenly. [power2dm.eu]

  The body attempts to remove the excess glucose through urination and the most common symptoms of type 2 diabetes include the following: Polydipsia (increased thirst) Polyphagia (increased hunger) Polyuria (increased frequency of urination), especially [news-medical.net]

• Nocturia

  ^ "Nocturia and nocturnal polyuria in men with lower urinary tract symptoms: oral desmopressin | key-points-from-the-evidence | Advice | NICE". www.nice.org.uk. Retrieved 2015-08-03. Further reading[edit] Movig, K. L. [en.wikipedia.org]

  Polyuria- Passing urine often or waking at night several times to pass urine (nocturia). Fatigue. Hunger. Weight loss. [healthengine.com.au]

  Characteristic features Classic Polyuria Secondary enuresis and nocturia in children Polydipsia Polyphagia Nonspecific Fatigue Visual disturbances: blurred vision Calf cramps Poor wound healing Pruritus Weight loss ; a thin appearance is typical for type [amboss.com]

  […] of symptoms of hyperglycaemia: fasting plasma glucose of ≥7.0 mmol/L plasma glucose of ≥11.1 mmol/L post-oral glucose tolerance test, with 1.75 g/kg (max 75g) of anhydrous glucose dissolved in water symptoms of diabetes, such as polyuria, polydipsia, nocturia [racgp.org.au]

  What is the patient’s immunization history - Eg, influenza, pneumococcal, hepatitis B, tetanus, herpes zoster As circumstances dictate, additional questions may be warranted, as follows: Does the patient give a history of recent polyuria, polydipsia, nocturia [emedicine.medscape.com]

• Vaginal Dryness

  Vaginal dryness in women and impotence in men are other complications of diabetes. Estimates suggest that between 35% and 70% of men with diabetes will eventually suffer from impotence. [onhealth.com]

• Headache

  There was no significant difference in the risk of cough, headache or hyperkalaemia when ARB was to placebo. On average risk of bias was judged to be either low (27% to 69%) or unclear (i.e. no information available) (8% to 73%). [dx.doi.org]

  The complications of diabetes type 2 include: heart palpitations excessive sweating slurred speech whiteness of skin confusion headache anxiety numbness in fingers, toes, and lips drowsiness More severe complications of diabetes type 2 include: diabetic [practo.com]

  Type 2 Diabetes Symptoms: Headaches Other symptoms that can occur if high blood sugar levels persist are fatigue, blurred vision, and headaches. [onhealth.com]

  Symptoms include: Being excessively thirsty Passing more urine Feeling tired and lethargic Always feeling hungry Having cuts that heal slowly Itching, skin infections Blurred vision Gradually putting on weight Mood swings Headaches Feeling dizzy Leg cramps [diabetesaustralia.com.au]

  […] early symptoms of low blood sugar include the following: Feeling weak Feeling dizzy Feeling hungry Trembling and feeling shaky Sweating Pounding heart Pale skin Feeling frightened or anxious Late symptoms of low blood sugar include: Feeling confused Headache [my.clevelandclinic.org]

• Paresthesia

  Nevertheless, there are some symptoms and signs that may indicate DM2: Lethargy Fatigue Weight loss Polyuria and polydipsia Paresthesias, pruritus Visual impairment Susceptibility to infection Retarded wound healing Detection of hyperglycemia during routine [symptoma.com]

  […] in the hands and feet, and itching Cardiovascular MI, stoke Eyes Retinal damage, blindness Legs/feet Nonhealing ulcers, cuts leading to gangrene and amputation Kidneys HTN, renal failure Neurology Paresthesias, neuropathy Diagnosis Serum glucose above [medical-dictionary.thefreedictionary.com]

  Other symptoms that may suggest hyperglycemia include blurred vision, lower extremity paresthesias, or yeast infections, particularly balanitis in men. [emedicine.medscape.com]

• Numbness of the Hand

  Common symptoms include the following: Frequent urination Excessive thirst Unexplained weight loss Extreme hunger Sudden vision changes Tingling or numbness in the hands or feet Feeling very tired much of the time Very dry skin Sores that are slow to [ucsfhealth.org]

  Being very thirsty Peeing a lot Blurry vision Being irritable Tingling or numbness in your hands or feet Feeling worn out Wounds that don't heal Yeast infections that keep coming back Continued Getting a Diagnosis Your doctor can test your blood for signs [webmd.com]

  People with type 2 diabetes may have the following signs and symptoms: blurred sight decreased sensation or numbness in the hands and feet dry, itchy skin frequent bladder and vaginal infections frequent need to urinate increased thirst and hunger male [medbroadcast.com]

Detection of hyperglycemia during routine screens is often the first hint at DM2. But although the measurement of blood glucose levels is a very sensitive approach to DM2 diagnosis, it is also very unspecific. Hyperglycemia may be induced by a variety of physiological and pathological conditions, the most common one being the recent ingestion of food. Thus, blood samples should be drawn from patients after overnight fasting. They should be collected in sodium fluoride tubes. Fasting glucose concentrations above 125 mg/dl are required for the diagnosis of DM.

Some patients who show unaltered fasting glucose levels, may nevertheless present impaired glucose tolerance. This condition may be considered a pre-diabetic pathology that should ensue therapy similar to manifest DM2. The World Health Organization (WHO) defines impaired glucose tolerance as "a state of higher than normal blood (or plasma) glucose concentration 2 hours after 75 gram oral glucose load" that does not meet criteria for DM, i.e., that surpasses 140 mg/dl, but not 200 mg/dl [10]. In case this value is > 200 mg/dl, the patient suffers from DM.

The aforementioned tests represent the current condition of the patient; in contrast, hemoglobin A1c (HbA1c) tests may be conducted to evaluate how well blood glucose levels were controlled during the last trimester. This test is often applied in DM2 diagnostics, but is of even greater importance during follow-ups: It shows if the patient responds well to therapy and/or if they comply with the therapeutic regimen.

Further diagnostic measures, e.g., ophthalmologic examination or urine analysis, are carried out to evaluate whether a DM2 patient is developing diabetic retinopathy, diabetic nephropathy or other complications.

• Ketonuria

  The more frequent ketonuria at initial diagnosis in Ab+ patients may be a reflection of the severity of beta-cell impairment. [doi.org]

  Characterized by hyperglycemia, glycosuria, polyuria, hyperlipemia (caused by imperfect catabolism of fats), acidosis, ketonuria, and a lowered resistance to infection. [medical-dictionary.thefreedictionary.com]

• Glucose Increased

  Fasting plasma glucose increased by 2.07 ± 0.82 mmol/L in the control group and 1.38 ± 0.81 mmol/L in the diet group. 2‐hour plasma glucose increased by 3.96 ± 0.89 mmol/L in the control group and 1.48 ± 0.94 mmol/L in the diet arm. [doi.org]

  Treatment options The main goal of treatment is to get your blood glucose (sugar) levels under control in order to increase your chances of a complication-free life. [wikidoc.org]

  Insulin deficiency causes reduced insulin-mediated glucose uptake from muscle, exaggerated glucose production from the liver, and increased free fatty acid mobilization from adipose tissue ( 3 ). [clinchem.aaccjnls.org]

  A focused diabetes history should also include the following questions: Is the patient's diabetes generally well controlled (with near-normal blood glucose levels) - Patients with poorly controlled blood glucose levels heal more slowly and are at increased [emedicine.medscape.com]

• Insulin Decreased

  The subsequent increase in insulin demand cannot be met by patients with insulin deficiency. A higher insulin dose is required. Decrease in insulin demand : vomiting and diarrhea lead to decreased glucose uptake, increasing the risk of hypoglycemia. [amboss.com]

• Streptococcus Pneumoniae

  All patients with diabetes mellitus should be vaccinated against Streptococcus pneumoniae (once) and influenza virus (annually). [msdmanuals.com]

Treatment aims at normalizing blood glucose levels and consists in lifestyle adaptations and medical therapy. With regards to the latter, several oral antidiabetic drugs are available. Metformin, a bioguanide, is most frequently prescribed as first-line treatment of DM2. Metformin counteracts peripheral insulin resistance and diminishes hepatic gluconeogenesis. Combination of metformin with other compounds may be required. Sulfonylureas and meglitinides, for instance, may supplement metformin therapy by stimulating pancreatic insulin release. Insulin administration is another option to this end. Decision aids have been developed to facilitate the selection of the most appropriate drug to combine with metformin [11].

Regular follow-ups are required to evaluate response to therapy. As has been indicated in the previous section, HbA1c tests are very helpful to this end.

DM2 may be associated with significant morbidity and - at least indirectly - mortality. Persistent hyperglycemia causes diabetic microangiopathy, which interferes with microcirculation and the respective pathophysiological development is assumed to account for severe complications like:

• Cardiovascular events, e.g., coronary artery disease, myocardial infarction and congestive heart failure, which are all associated with rather poor prognoses
• Diabetic foot ulcer, a leading cause of lower limb amputation
• Diabetic nephropathy, which may eventually lead to end-stage renal disease
• Diabetic neuropathy, a condition predisposing for diabetic foot ulcer
• Diabetic retinopathy, a common cause of blindness

In sum, the average reduction of life expectancy has been estimated to be about eight years [2]. An adequate control of blood glucose levels is the key to risk minimization and can only be achieved if patients understand the importance of compliance. Further improvement of prognosis can be attained by intensive treatment of accompanying cardiovascular risk factors [9].

DM2 is a multifactorial disease; and while several risk factors have been identified to date, there are still considerable knowledge gaps regarding the etiology and pathogenesis of this disorder. According to current knowledge, both genetic predisposition [3] and lifestyle decisions contribute to hyperglycemia, preferentially in patients aged 50 years an older. Additionally, DM2 and other civilization diseases are frequently mutually dependent.

In detail, the following factors favor the development of DM2:

• Family history of DM2
• Medical history of gestational DM (patient or their mother)
• Ethnicity (Blacks, Asians and Hispanics)
• Older age
• High-caloric diet
• Lack of exercise
• Overweight and obesity
• Hypertension
• Atherogenic dyslipidemia (hypercholesteremia, hypertriglyceridemia)
• Polycystic ovary syndrome

Cut-off values can hardly be defined. The more severe a certain pathology, the higher the increase of risk of DM2. With regards to overweight and obesity, for instance, people with a body mass index (BMI) > 25 have been shown to have a 3-fold augmented risk of developing DM2. In contrast, those individuals whose BMI > 30 present a 10-fold increased risk [4].

It has been reported that neuropsychiatric disorders are more prevalent among DM2 patients than among the general population. Thus, depression, schizophrenia and similar diseases are sometimes named as risk factors for DM2. In the light of recent findings though, neuropsychiatric disorders are rather assumed to be consequences of DM2 than causes [5].

As has been indicated in the previous section, the individual risk of developing DM2 increases with age. Available epidemiological data confirm that DM2 is most commonly diagnosed in patients aged 40 to 60 years, but they also show that the average age of onset is decreasing. Such developments are presumably due to lifestyle changes and an increased prevalence of other risk factors, e.g., of poor diets, overweight/obesity and lack of exercise. Data representing the current situation in the United States shall be mentioned exemplarily [2]:

• Lifetime risks of developing DM2 range from 33% in women to 39% in men.
• Prevalence peaks in people aged > 60 years, and in this age group, a total of 67% is assumed to suffer from manifest DM2 or pre-diabetic conditions.
• About 69% of US-American adults are overweight or obese.
• With respect to the elderly, 73% of all women and 77% of all men have BMI > 25.
• Increasing tendencies are noted for all these values.

The latter statement also applies for countries that are not considered part of the Western world. Here, adoption of unhealthy diets contributes to rising incidence and prevalence of DM2. To date, the overall values are much lower, though [6].

Both peripheral insulin resistance, i.e., a diminished response to insulin release, as well as a reduction of insulin synthesis in pancreatic β cells accounts for the onset of persistent hyperglycemia in DM2 patients.

To date, the pathogenesis of insulin resistance is not well understood. Similar to DM2 itself, this condition is presumably multifactorial. Insulin receptors are tyrosine kinase receptors and consist of α and β subunits. Upon binding of insulin, phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways are activated and mediate distinct effects. In DM2 patients, PI3K-dependent signaling cascades are insufficiently stimulated [7], which results in a reduction of glucose and potassium uptake by myocytes, hepatocytes, adipocytes and other cell types. This initial stage of the disease is marked by hyperglycemia and normoinsulinemia.

In an attempt to overcome this condition, synthesis and release of insulin by pancreatic β cells is stimulated further. Because of the underlying insulin resistance, blood glucose levels cannot be normalized and hyperglycemia and hyperinsulinemia develops. This condition is rarely recognized before β cell exhaustion sets in. Insulin-producing cells are unable to keep up with the persistent demand for hormone release and finally, patients show deficient insulin production and hypoinsulinemia. Only the combination of insulin resistance and secretion deficit trigger the onset of DM2 [8].

Several preventive measures can be deducted from the above given list of risk factors for DM2. In general, maintenance of a healthy, balanced diet, regular exercise and avoidance of overweight and obesity go a long way towards reducing the individual risk of developing this chronic disease. Such measures have both direct and indirect effects, i.e., they also contribute to diminish hypertension, dyslipidemia and atherosclerosis, and these pathologies are, in turn, risk factors for DM2.

Patients should be advised about the severity of DM2. Hyperglycemia is not painful and symptoms may not manifest in years, which is why large parts of the population underestimate the morbidity associated with that condition. Many people have heard about diabetic retinopathy, diabetic nephropathy and diabetic food ulcer, but may chose not to adhere to recommendations regarding prevention or therapy since they are currently feeling well.

In case of manifest DM2, compliance with the therapeutic regimen is of utmost importance to decrease the risk of severe complications of the disease. However, medical treatment should never be a substitute for lifestyle adaptation.

Diabetes mellitus (DM) is a very common metabolic disorder characterized by permanently increased blood glucose levels. Distinct types of DM have been described, according to the pathomechanisms that cause hyperglycemia.

Under physiological conditions, high serum concentrations of glucose trigger insulin release from pancreatic β cells. Subsequently, insulin binds to cell surface receptors expressed by a variety of distinct tissues and thus mediates the influx of glucose and potassium ions. This way, cells are supplied with the most important substrate for glycolysis and generation of ATP, and blood glucose levels are decreased.

Hyperglycemia may result from distinct disturbances of the chain of events described above. For instance, the overall amount of insulin released by β cells may be reduced because of an autoimmune reaction against those cells. This is the case in diabetes mellitus type 1 (DM1). On the other hand, its target cells may lose their susceptibility to insulin and despite satisfactory release of this hormone, blood glucose concentrations cannot be diminished to physiological values. This is characteristic for diabetes mellitus type 2 (DM2). Of note, there are several additional types of DM that may be related to hereditary dysfunction of β cells or peripheral resistance to insulin, pancreatic diseases [1], or the effects of other hormones or drugs. DM2 is by far the most prevalent type of DM.

Adequate regulation of blood glucose levels may be a real challenge and both severe hyperglycemia and hypoglycemia may have detrimental consequences in the short term. Fortunately, only minor shares of DM2 patients present in a life-threatening hyperosmolar hyperglycemic state, with diabetic coma or hypoglycemic coma. However, large parts of the elder population have to face long-term sequelae of permanently increased concentrations of blood glucose: diabetic retinopathy, diabetic nephropathy and diabetic food ulcer are only examples for severe complications of DM2 [2]. These and other DM2-related pathologies account for the high morbidity associated with this disease.

Diabetes mellitus type 2 (DM2) is a metabolic disorder characterized by permanently increased blood glucose levels. This condition is mainly the result of peripheral insulin resistance and reduced insulin release by pancreatic β cells. The term peripheral insulin resistance refers to the inability of insulin to mediate glucose uptake into cells of muscles, liver and other tissues. Consequently, blood glucose concentrations remain high, and pancreatic β cells are continuously stimulated to release more insulin. Eventually, this causes β cell exhaustion and lack of insulin. Thus, DM2 patients typically show hyperglycemia and hypoinsulinemia.

DM2 is a prime example for what is commonly called a civilization disease. Thereby, it is put on the same footing as hypertension, atherosclerosis and hypercholesteremia. And in fact, these diseases share many risk factors - and while some of them are beyond the patient's control, others can be prevented by taking the corresponding lifestyle decisions. In detail, the following pathologies have been identified as risk factors of DM2:

• Family history of DM2
• Medical history of gestational DM (patient or their mother)
• Older age
• High-caloric diet
• Lack of exercise
• Overweight and obesity
• Hypertension
• Atherogenic dyslipidemia (hypercholesteremia, hypertriglyceridemia)

Adaptations of lifestyle and compliance with therapeutic regimens is of utmost importance to delay disease progression and to minimize the risk of severe, potentially life-threatening complications like myocardial infarction, diabetic foot ulcer, end-stage renal disease and blindness. Medical treatment should always be considered a supplement of lifestyle adjustments, not a substitute of the latter.

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2. Gray N, Picone G, Sloan F, Yashkin A. Relation between BMI and diabetes mellitus and its complications among US older adults. South Med J. 2015; 108(1):29-36.
3. Fuchsberger C, Flannick J, Teslovich TM, et al. The genetic architecture of type 2 diabetes. Nature. 2016.
4. Bonora E, Kiechl S, Willeit J, et al. Population-based incidence rates and risk factors for type 2 diabetes in white individuals: the Bruneck study. Diabetes. 2004; 53(7):1782-1789.
5. Lunghi C, Moisan J, Gregoire JP, Guenette L. Incidence of Depression and Associated Factors in Patients With Type 2 Diabetes in Quebec, Canada: A Population-Based Cohort Study. Medicine (Baltimore). 2016; 95(21):e3514.
6. Sabir A, Ohwovoriole A, Isezuo S, Fasanmade O, Abubakar S, Iwuala S. Type 2 diabetes mellitus and its risk factors among the rural Fulanis of Northern Nigeria. Ann Afr Med. 2013; 12(4):217-222.
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8. Carrera Boada CA, Martinez-Moreno JM. Pathophysiology of diabetes mellitus type 2: beyond the duo "insulin resistance-secretion deficit". Nutr Hosp. 2013; 28 Suppl 2:78-87.
9. Griffin SJ, Borch-Johnsen K, Davies MJ, et al. Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial. Lancet. 2011; 378(9786):156-167.
10. World Health Organization. About diabetes. Diabetes Programm. 2016; http://www.who.int/diabetes/action_online/basics/en/index2.html. Accessed 15th July, 2016.
11. Shillington AC, Col N, Bailey RA, Jewell MA. Development of a patient decision aid for type 2 diabetes mellitus for patients not achieving glycemic control on metformin alone. Patient Prefer Adherence. 2015; 9:609-617.