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Query: UMLS:C0011860 (type 2 diabetes)
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Metformin is a biguanide commonly used in type 2 diabetes and considered to be a safe drug with minimal side effects. Approximately 2% of cases of acute pancreatitis may be caused by drugs, but it is not a known complication of metformin therapy. To date only one case of pancreatitis has been reported in association with metformin, but that was secondary to metformin poisoning (overdose). This is the first reported case of pancreatitis caused by a therapeutic dose of metformin (although in this case renal failure precipitated the metformin toxicity). Severe lactic acidosis is a rare but life threatening complication of metformin, which occurs particularly in patients with renal failure.
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PMID:Metformin induced acute pancreatitis precipitated by renal failure. 1508 49

There is evidence for the role of genetic and environmental factors in feline and canine diabetes. Type 2 diabetes is the most common form of diabetes in cats. Evidence for genetic factors in feline diabetes includes the overrepresentation of Burmese cats with diabetes. Environmental risk factors in domestic or Burmese cats include advancing age, obesity, male gender, neutering, drug treatment, physical inactivity, and indoor confinement. High-carbohydrate diets increase blood glucose and insulin levels and may predispose cats to obesity and diabetes. Low-carbohydrate, high-protein diets may help prevent diabetes in cats at risk such as obese cats or lean cats with underlying low insulin sensitivity. Evidence exists for a genetic basis and altered immune response in the pathogenesis of canine diabetes. Seasonal effects on the incidence of diagnosis indicate that there are environmental influences on disease progression. At least 50% of diabetic dogs have type 1 diabetes based on present evidence of immune destruction of beta-cells. Epidemiological factors closely match those of the latent autoimmune diabetes of adults form of human type 1 diabetes. Extensive pancreatic damage, likely from chronic pancreatitis, causes approximately 28% of canine diabetes cases. Environmental factors such as feeding of high-fat diets are potentially associated with pancreatitis and likely play a role in the development of pancreatitis in diabetic dogs. There are no published data showing that overt type 2 diabetes occurs in dogs or that obesity is a risk factor for canine diabetes. Diabetes diagnosed in a bitch during either pregnancy or diestrus is comparable to human gestational diabetes.
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PMID:Canine and feline diabetes mellitus: nature or nurture? 1528 6

Mixed dyslipidaemia is common in people with diabetes and occurs in up to 20% of cases. Diabetes keto-acidosis can occur in patients with type 2 diabetes. Hypertriglyceridaemia is a well-recognised cause of pancreatitis. Other common causes of pancreatitis include gall stones, alcohol, drugs (azathioprine and dideoxyinosine) and post-endoscopic retrograde cholangiopancreatography (ERCP). Therapeutic options for acute and severe dyslipidaemia include insulin therapy, fibric acid derivatives, fish oils and, rarely, nicotinic acids. Hospitalisation may be required for plasmapheresis in specialised centres.
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PMID:Test and teach. Number Fifty-three. Diagnosis: Diabetes-related dyslipidaemia. 1584 94

Diabetic ketoacidosis (DKA) is the most common hyperglycemic emergency in patients with diabetes mellitus. DKA most often occurs in patients with type 1 diabetes, but patients with type 2 diabetes are susceptible to DKA under stressful conditions, such as trauma, surgery, or infections. DKA is reported to be responsible for more than 100 000 hospital admissions per year in the US, and accounts for 4-9% of all hospital discharge summaries among patients with diabetes. Treatment of patients with DKA uses significant healthcare resources and accounts for 1 out of every 4 healthcare dollars spent on direct medical care for adult patients with type 1 diabetes in the US. Recent studies using standardized written guidelines for therapy have demonstrated a mortality rate of less than 5%, with higher mortality rates observed in elderly patients and those with concomitant life-threatening illnesses. Worldwide, infection is the most common precipitating cause for DKA, occurring in 30-50% of cases. Urinary tract infection and pneumonia account for the majority of infections. Other precipitating causes are intercurrent illnesses (i.e., surgery, trauma, myocardial ischemia, pancreatitis), psychological stress, and non-compliance with insulin therapy. The triad of uncontrolled hyperglycemia, metabolic acidosis and increased total body ketone concentration characterizes DKA. These metabolic derangements result from the combination of absolute or relative insulin deficiency and increased levels of counter-regulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). Successful treatment of DKA requires frequent monitoring of patients, correction of hypovolemia and hyperglycemia, replacement of electrolyte losses, and careful search for the precipitating cause. Since the majority of DKA cases occur in patients with a known history of diabetes, this acute metabolic complication should be largely preventable through early detection, and by the education of patients, healthcare professionals, and the general public. The frequency of hospitalizations for DKA has been reduced following diabetes education programs, improved follow-up care, and access to medical advice. Novel approaches to patient education incorporating a variety of healthcare beliefs and socioeconomic issues are critical to an effective prevention program.
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PMID:Diabetic ketoacidosis: risk factors and management strategies. 1587 46

As an example of iatrogenic diabetes, we discuss the problem of diabetes mellitus in patients receiving atypical antipsychotics. The risk of diabetes mellitus appears to be different according to various molecules with, by decreasing order, clozapine, olanzapine, risperidone and quetiapine, and finally amisulpride, aripiprazole and ziprasidone. A careful analysis of published case reports and series indicates the existence of two different problems: 1) the rather common development of impaired glucose tolerance or diabetes mellitus (often associated with metabolic syndrome) related to weight gain in individuals at risk for type 2 diabetes; and 2) the occurrence of rare cases of acute metabolic episodes with severe ketoacidosis and/or pancreatitis whose pathophysiological mechanisms remain largely unknown. Generally speaking, the pathophysiology involves both increased insulin resistance and deficient insulin secretion. Cautious metabolic monitoring of patients receiving atypical antipsychotics is recommended, and the selection of the appropriate drug should be influenced by the metabolic profile of the various molecules and the metabolic risk of the patients who should be treated with atypical antipsychotics.
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PMID:[Drug-induced diabetes mellitus: the exemple of atypical antipsychotics]. 1603 11

Xanthoma and xanthelasma are typical symptoms of lipid and lipoprotein metabolism impairment. On the basis of their incidence and morphology, it is even possible to specify the impairment type. Hypercholesterolemia or certain liver dysfunctions are characterized by slow development of surface xanthelasmas usually located on mechanically stressed regions (e.g. eyelids). Tuberous and tendinous xanthomas are typical for familiar hypercholesterolemia and are common symptoms of homozygous familiar hypercholesterolemia. Small and quickly developing eruptive xanthomas are typical for mixed hyperlipoproteinemia (secondary hyperlipoproteinemia is typical for diabetes). Mechanism of accumulation of lipids in skin morphs is similar to the development of atheroma, especially when talking about the role of modified LDL and the way of accumulation of lipids in macrophages. The following factors are very important for etiopathogenesis of skin xanthomas development: mechanical stress of tissues, increased permeability of skin capillaries and reaction of proteoglycans in sparse connective tissue. Xanthomas and xanthelasmas are typical indicators of other complicating diseases as e.g. development of acute pancreatitis during hyperlipoproteinemic crisis, aggravation of insulin resistance, and decompensation of type 2 diabetes mellitus. The therapy focuses on adjustment of dietary regime (elimination of dietary fat and concentrated saccharides); no food and sufficient hydration via infusion of crystalloid solutions is indicated in cases of serious hyperlipoproteinemic crisis. In vital indication, it is possible to perform repeated plasmapheresis (or better continual plasmapheresis) that can correct even serious hyperlipoproteinemic crises within several hours. And what is more, continual plasmapheresis can significantly reduce the period when hyperlipoproteinemic crisis might induce acute necrotizing pancreatitis. In the long run, we require that patients strictly observe their dietary regime based on the type of hyperlipoproteinemia. As for medicamentous therapy, fibrates and atorvastatin (from statin family) are the preparations of choice. It is very important not to focus on symptoms, i.e. xanthoma or xanthelasma, but fully compensate lipid metabolism impairment or the disease that underlies hyperlipoproteinemia (e.g. type 2 diabetes mellitus or metabolic syndrome). Unfortunately, it still can be seen that dermatologists, ophthalmologists or plastic surgeons remove extensive xanthelasmas, while the underlying cause is not approached diagnostically and therapeutically at all.
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PMID:[Internist's view on skin manifestations of hyperlipidemia in diabetic patients]. 1677 Oct 91

Lipodystrophies represent a heterogeneous group of diseases characterized by an abnormal subcutaneous fat distribution, the extent of which can vary from localized, to partial, to generalized lipoatrophy. Whereas partial and generalized lipodystrophies are each associated with metabolic abnormalities, the localized form is not. These metabolic changes include insulin resistance with type 2 diabetes, acanthosis nigricans, dyslipidaemia predominantly consisting of hypertriglyceridaemia (associated with the onset of pancreatitis) and depressed HDL cholesterol, liver steatosis and hypertension. Affected women are often hirsute and this can be associated with the presence of polycystic ovarian syndrome (PCOS). Most of these clinical features are present to some extent in patients with the common metabolic syndrome. As the prevalence of metabolic syndrome far outweighs that of lipodystrophy, the diagnosis of this rare disorder may often be overlooked with the affected patient diagnosed as merely being 'yet' another case of metabolic syndrome. In this article, we draw attention to the importance of recognizing patients with lipodystrophy who present with metabolic abnormalities, as both the diagnostic as well as the therapeutic approach of these patients differ profoundly from patients with the metabolic syndrome.
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PMID:Inherited lipodystrophies and the metabolic syndrome. 1756 81

The capsaicin receptor transient receptor potential vanilloid subfamily member 1 (TRPV1) is highly expressed on sensory nerve fibers innervating the pancreas. Indeed, the role of TRPV1 in mediating pain during pancreatitis is well established. The initial excitation of these nerves by capsaicin is followed by a reversible refractory state (desensitization) or, under certain conditions such as neonatal treatment, neurotoxicity. Interestingly, ablation of TRPV1-positive fibers by subcutaneous capsaicin treatment not only ameliorates pancreatitis pain but also diminishes aging-associated weight gain and improves glucose tolerance both in mice on a high-fat diet and in rat models of type 2 diabetes. New evidence implies an unexpected, pivotal role for TRPV1 in type 1 (autoimmune) diabetes. Non-obese diabetic (NOD) mice carry a hypofunctional TRPV1 mutant. Ablation of nerves carrying this mutant TRPV1 by capsaicin prevents immune-mediated destruction of islet beta cells despite the persistence of diabetogenic T cells. Collectively, these findings establish a crucial link among sensory nerves, obesity and diabetes and identify pharmacological TRPV1 blockade as a novel therapeutic approach for diabetes prevention and weight control.
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PMID:The emerging role of TRPV1 in diabetes and obesity. 1805 25

Oral therapy for type 2 diabetes mellitus, when used appropriately, can safely assist patients to achieve glycaemic targets in the short to medium term. However, the progressive nature of type 2 diabetes usually requires a combination of two or more oral agents in the longer term, often as a prelude to insulin therapy. Issues of safety and tolerability, notably weight gain, often limit the optimal application of anti-diabetic drugs such as sulfonylureas and thiazolidinediones. Moreover, the impact of different drugs, even within a single class, on the risk of long-term vascular complications has come under scrutiny. For example, recent publication of evidence suggesting potential detrimental effects of rosiglitazone on myocardial events generated a heated debate and led to a reduction in use of this drug. In contrast, current evidence supports the view that pioglitazone has vasculoprotective properties. Both drugs are contraindicated in patients who are at risk of heart failure. An additional recently identified safety concern is an increased risk of fractures, especially in postmenopausal women.Several new drugs with glucose-lowering efficacy that may offer certain advantages have recently become available. These include (i) injectable glucagon-like peptide-1 (GLP-1) receptor agonists and oral dipeptidyl peptidase-4 (DPP-4) inhibitors; (ii) the amylin analogue pramlintide; and (iii) selective cannabinoid receptor-1 (CB1) antagonists. GLP-1 receptor agonists, such as exenatide, stimulate nutrient-induced insulin secretion and reduce inappropriate glucagon secretion while delaying gastric emptying and reducing appetite. These agents offer a low risk of hypoglycaemia combined with sustained weight loss. The DPP-4 inhibitors sitagliptin and vildagliptin are generally weight neutral, with less marked gastrointestinal adverse effects than the GLP-1 receptor agonists. Potential benefits of GLP-1 receptor stimulation on beta cell neogenesis are under investigation. Pancreatitis has been reported in exenatide-treated patients. Pramlintide, an injected peptide used in combination with insulin, can reduce insulin dose and bodyweight. The CB1 receptor antagonist rimonabant promotes weight loss and has favourable effects on aspects of the metabolic syndrome, including the hyperglycaemia of type 2 diabetes. However, in 2007 the US FDA declined approval of rimonabant, requiring more data on adverse effects, notably depression. The future of dual peroxisome proliferator-activated receptor-alpha/gamma agonists, or glitazars, is presently uncertain following concerns about their safety.In conclusion, several new classes of drugs have recently become available in some countries that offer new options for treating type 2 diabetes. Beneficial or neutral effects on bodyweight are an attractive feature of the new drugs. However, the higher cost of these agents, coupled with an absence of long-term safety and clinical outcome data, need to be taken into consideration by clinicians and healthcare organizations.
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PMID:New drugs for type 2 diabetes mellitus: what is their place in therapy? 1884 4

TREATMENT OF ARTERIAL HYPERTENSION - Blood pressure (BP) should be regularly measured in all patients with CKD (Strength of Recommendation C). - BP control and proteinuria reduction delay progression of CKD (Strength of Recommendation A) and reduce cardiovascular risk (Strength of Recommendation C). Thus, control of both factors should be the treatment objective. - The BP target in patients with CKD should be < 130/80 mmHg, and 125/75 mmHg if proteinuria is > 1 g/24 hours (Strength of Recommendation A). - Lifestyle changes should be made: low-sodium diet (less than 100 mEq/day of sodium or 2.4 g/day of salt); weight reduction if patient is overweight (body mass index 20-25 kg/m2); regular aerobic physical exercise and moderate alcohol intake for BP control and prevention of cardiovascular risk (Strength of Recommendation A). - The choice of the antihypertensive drug in patients with CKD depends on the etiology of CKD, cardiovascular risk, or presence of clinical or subclinical cardiovascular disease (Strength of Recommendation A). - Two or more antihypertensive drugs are usually required to control blood pressure in patients with CKD (Strength of Recommendation B), and will frequently include a diuretic, which in stages 4-5 should be a loop diuretic (Strength of Recommendation B). - Renin-angiotensin-aldosterone system (RAAS) inhibitors are first choice drugs in patients with diabetic nephropathy, patients with non-diabetic nephropathy with a protein/creatinine ratio higher than 200 mg/g, and patients with heart failure (Strength of Recommendation A). The combination of ACEIs and ARBs is indicated for reducing proteinuria that remains high despite treatment with a RAAS inhibitor, provided potassium levels do not exceed 5.5 mEq/L (Strength of Recommendation B). - When RAAS blockers are started or their dose is changed in patients with advanced CKD, kidney function and serum potassium levels should be monitored at least after 1-2 weeks. DIAGNOSIS AND TREATMENT OF DYSLIPIDEMIA - A complete evaluation of the lipid profile including total cholesterol, LDL-C, HDL-C, and triglycerides should be performed in any patient with CKD at baseline and at least annually (Strength of Recommendation B). - In patients with stage 4-5 CKD and LDL-C >or= 100 mg/dL, treatment to decrease levels to < 100 mg/dL should be considered because of their high CV risk. This reduction is recommended in secondary prevention and in primary prevention in diabetic patients. Lipid-lowering treatment is recommended in all other patients, although no evidence showing its benefits is available yet (Strength of Recommendation C). - In patients with stage 4-5 CKD and triglyceride levels >or= 500 mg/dL which are not corrected by treating the underlying cases, treatment with triglyceride-lowering drugs may be considered to reduce the risk of pancreatitis. However, treatment with fibrates should be used with caution, and these drugs should not be associated to statins due to the risk of rhabdomyolysis (Strength of Recommendation C). There is little experience on the efficacy and safety of omega-3 fatty acids for the treatment of hypertriglyceridemia in patients with grade 4-5 CRF, but they may be considered a possibly safer alternative to fibrates (Strength of Recommendation C). SMOKING - Smoking is a cardiovascular risk factor and a risk factor for progression of kidney disease in patients with CRF (Strength of Recommendation B). - Use of active measures to achieve smoking cessation is recommended in patients with CRF (Strength of Recommendation C). HOMOCYSTEINE - Hyperhomocysteinemia has been postulated as a cardiovascular risk factor in the general population and in kidney patients, but the available evidence is not consistent. - There is no evidence that vitamin therapy decreases cardiovascular risk in patients with CRF, and recommendation of routine vitamin measurement and start of vitamin therapy to reduce cardiovascular risk in these patients is therefore questionable (Strength of Recommendation B). LEFT VENTRICULAR HYPERTROPHY - Left ventricular hypertrophy (LVH) is a cardiovascular risk factor in patients with CRF (Strength of Recommendation B). - It is advisable to perform an echocardiogram at baseline and every 12-24 months and to consider treatments allowing for LVH regression (Strength of Recommendation C). The approach to LVH should be early and multifactorial because its reversibility is limited once established (Strength of Recommendation C). - RAAS blockade with ACEIs or ARBs partially reverts LVH in patients with CRF (Strength of Recommendation B). ANTI-PLATELET AGGREGATION - Because of the high cardiovascular risk in patients with CKD, anti-platelet aggregant therapy, especially low-dose aspirin, would be indicated in patients with type 2 diabetes as primary prevention, and in all patients with CKD as secondary prevention. There is however no evidence of the benefits of anti-platelet aggregant therapy in primary prevention in patients with CKD, particularly in stages 4-5; indication for treatment in this situation should therefore be individualised because of its greater risk of bleeding. - Adequate good blood pressure control should previously be achieved to minimise the risk of haemorrhagic stroke (Strength of Recommendation C).
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PMID:[Arterial hypertension and dyslipidemia in patients with chronic kidney disease (CKD). Anti-platelet aggregation. Goal oriented treatment]. 1901 37

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