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Scientific highlights from Diabetes and thyroid disorders in clinical practice today: progresses and challenges

Scientific highlights from Diabetes and thyroid disorders in clinical practice today: progresses and challenges
  • Endocrinology and metabolism
  • Thyroid disorder

Resource type

Publication

Tags

Diabetes and thyroid disorders in clinical practice today (Rome Italy 2014)
Pre-diabetes
Managing pre-diabetes
benign thyroid nodules
nodules
Percutaneous ethanol injection (PEI)
Ultrasound-guided interstitial laser therapy
thyroid nodular disease
Radiofrequency ablation (RFA)
Cardiovascular implications
Metabolic syndrome
subclinical hypothyroidism
Treating subclinical hypothyroidism
Diabetes in pregnancy
GDM
Managing GDM
Gestational diabetes mellitus (GDM)

Improving global clinical management of diabetes and thyroid disorders

Healthcare professionals from a range of countries attended this dynamic one-day conference on type 2 diabetes mellitus and thyroid disorder (TD) management. Workshop and didactic presentations looked at ways to address the many clinical challenges associated with these highly prevalent, chronic conditions.

Overview

Type 2 diabetes is an increasing global problem, particularly in regions where rates of obesity, sedentary lifestyles, smoking and ‘fast food’ consumption are high or rising. Complications and comorbidities of type 2 diabetes are a growing burden for local healthcare systems: there are few standardised guidelines for its care and management, and limited infrastructure and economic resources.TD are very common in emerging nations, because of iodine deficiency and genetic factors that lead to goitre and gland dysfunctions. Hypothyroidism, thyroid nodules and thyroid cancer are frequently observed in developing countries. Globally, local healthcare systems often benefit from tailored medical education that follows the principles of international guidelines or standards of care.

Managing pre-diabetes: lifestyle first but drugs work

Professor David Leslie (St Bartholomew’s Hospital and The Blizard Institute, London, UK) and Dr Lelio Morviducci (San Camillo Hospital, Rome, Italy) debated whether to treat pre-diabetes with a dietary or drug-focused approach Lifestyle modification remains the best way to help prevent the development of type 2 diabetes, but drug-treatment strategies are crucial for situations when lifestyle interventions fail.

Both speakers emphasized that prevention of type 2 diabetes is of primary importance for the clinical team.

Offering prevention strategies clearly helps to reduce the number of people who develop the disease
These strategies also limit the medical, personal and cost burden of diabetes-associated complications

Research has been undertaken in large-scale trials, to try and identify the best approaches for preventing the onset of type 2 diabetes in people at high risk of developing the disease.

Lifestyle modification involving calorie-restricted, ‘healthy eating’ diets and scheduled physical activity offers the most effective approach to reduce the risk of diabetes development. However, it can be challenging for people at risk of type 2 diabetes to change their behaviour enough to maintain new patterns of eating and exercise over the long term.

Figure 1 shows how, in major studies of diabetes prevention, at best a 58% reduction in diabetes development has been observed.

Figure 1: Relative risk reduction (%) of new-onset type 2 diabetes in randomized, controlled clinical trials of prevention

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Da Qing (Pan et al, Diabetes Care 1997); Finnish Diabetes Prevention Study, Tuomilehto et al, N Engl J Med 2001; DPP, Diabetes prevention programme (Ratner et al,   et al Endocrin Pract, 2006) STOP-NIDDM, Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (Chiasson, Endocrin Pract, 2006); DREAM (Gerstein, Lancet, 2006); TRIPOD, XENDOS, RAS Blockade (Chiasson, Endocrinol 2005)

Drug treatment

Good results have been obtained when anti-diabetic drugs have been used for the prevention of diabetes in high-risk people. In clinical-trial settings, participants often maintain sufficient therapeutic compliance to keep diabetes at bay.

Beneficial effects of specific oral anti-diabetic drugs in people at high risk of diabetes can be summarized as follows:

  • Reducing blood glucose levels (alpha glucosidase inhibitors [e.g. acarbose])
  • Increasing sensitivity of liver to the uptake/effects of insulin (biguanides [e.g. metformin)
  • Determining body-fat redistribution with additional effects on insulin sensitivity and partially on beta-cells (thiazolidenediones [TZDs; e.g. pioglitazone])
  • Restoring first-phase insulin secretion (glinides [e.g. repaglinide])
  • Reducing body weight (lipase inhibitors [e.g. orlistat])

 

In specific subgroups, metformin is as effective as lifestyle intervention in reducing cumulative diabetes incidence, although TZDs show the highest reductions (Figure 2).

Figure 2: Summary of the absolute risk reduction of developing diabetes over time, using lifestyle modification and anti-diabetic drugs

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DPS, Finnish Diabetes Prevention Study, Tuomilehto et al, N Engl J Med 2001; DPP, Diabetes prevention programme (Ratner et al,   et al Endocrin Pract, 2006) TRIPOD, XENDOS, RAS Blockade (Chiasson, Endocrinol 2005); STOP-NIDDM, Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (Chiasson, Endocrin Pract, 2006)

Non-surgical interventions: efficacious for thyroid nodular disease

Dr Laszlo Hegedüs (Odense University Hospital/University of Southern Denmark, Denmark) described how medical therapy and ultrasound-guided interventions have simplified the management of symptomatic benign thyroid nodules

Medical therapy and ultrasound-guided interventions are good alternatives to standard surgery, for patients with benign thyroid nodular disease. Several minimally invasive strategies have been developed, with treatment selection based on the type of nodule (Figure 3).  Dr Hegedüs described the options in detail.

Excellent results have been obtained with PEI as a non-surgical strategy for cystic nodule management:

  • PEI can be performed in outpatient clinics and presents no radiation hazard
  • Following treatment, histological changes occur that gradually lead to progressive shrinkage of the cyst cavity
  • To date, there are no safety concerns with these procedures and no extrathyroidal effects; ‘mild’ side-effects occur in <10% of patients

 

Figure 3: Innovative non-surgical strategies for the management of benign thyroid nodular disease. FNAB, fine-needle aspiration biopsy; ILP, interstitial laser photocoagulation; PEI, percutaneous ethanol injection; RFA, radiofrequency ablation; TSH, thyroid stimulating hormone; US, ultrasound

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Percutaneous ethanol injection

Excellent results have been obtained with PEI as a non-surgical strategy for cystic nodule management:

  • PEI can be performed in outpatient clinics and presents no radiation hazard
  • Following treatment, histological changes occur that gradually lead to progressive shrinkage of the cyst cavity
  • To date, there are no safety concerns with these procedures and no extrathyroidal effects; ‘mild’ side-effects occur in <10% of patients

 

Ultrasound-guided interstitial laser therapy

For solid nodules, ultrasound-guided interstitial laser therapy can be performed in outpatient centres:

This therapy regimen is associated with favourable safety, cost and efficacy results (far higher than those seen for LT4 therapy)
Significant volume reductions have been observed 6 and 12 months after therapy, compared with no intervention

Although there is a fairly high recurrence rate (likely above 30%), ultrasound-guided interstitial laser therapy is easily repeatable, added Dr Hegedüs. Pain was reported as mild and short-term by 86% of patients, although more serious side effects have been occasionally reported.

Radiofrequency ablation

Radiofrequency ablation also has a good safety and efficacy profile in patients with functioning and non-functioning benign thyroid nodules:

Shrinkage rates are 50% (one treatment), rising above 80% (repeated treatments)
Although radiofrequency ablation must be performed under conscious sedation, less postprocedural pain is reported by patients.

Dr Hegedüs cautioned that this procedure is only available in selected centres and must be performed by clinicians skilled in interventional US.

There is a need for randomized studies and head-to-head comparison with other procedures. The long-term efficacy of radiofrequency ablation remains to be proven.

Cardiovascular diseases and diabetes: close association requires investigation

[Copy for photo legends/call-outs] Dr Eberhard Standl (Munich Diabetes Research Group, Helmholtz Centre, Munich, Germany) characterized the association between cardiovascular disease and the altered metabolic function seen in type 2 diabetes

The close relationship between cardiovascular disease and diabetes means patients with one of the conditions should routinely be screened for the other, said Dr Standl.

  • Prompt identification of problems enables treatment to be initiated quickly
  • Closely controlling glycemia, lipid and blood-pressure levels helps to prevent coronary ischaemic disease and reduce stroke incidence of stroke

 

Dr Standl highlighted the risks and how to screen for them:

  • Patients with diabetes are at very high or high risk of cardiovascular disease, depending on the presence of concomitant risk factors and target organ damage
  • Urinary albumin excretion rate should be estimated when performing risk stratification
  • Screening for silent myocardial ischaemia may be considered, in selected high-risk patients

 

In many studies of heart disease, hyperglycaemia is a common and often undiagnosed condition. (Figure 3).

Figure 4: Hyperglycaemia is often undiagnosed in patients with coronary artery disease

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Managing metabolic alterations

Diabetes is closely associated with cardiovascular disease development, due to the metabolic alterations that occur.

These include hyperglycemia, dyslipidemia, hypertension, endothelial dysfunction, prothrombotic state, chronic inflammation, autonomic dysfunction, accelerated atherosclerosis

Metabolic syndrome carries double the relative risk of cardiovascular disease and five times the relative risk of type 2 diabetes
Metabolic system also confers a high risk for fatty liver disease, obstructive sleep apnoea, gallstones and polycystic ovarian syndrome

Dr Standl reminded clinicians to be alert for insulin resistance and metabolic syndrome in patients who have several key risk factors. (listed in Fig. 4)

Figure 5: Metabolic syndrome and insulin resistance: associated diseases

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Treatment targets

Treatment targets for the multifactorial management of type 2 diabetes were also described by Dr Standl.

Table 1: Treatment targets for multifactorial management of type 2 diabetes

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Treating subclinical hypothyroidism

Dr B Biondi and Dr Salman Razvi (Queen Elizabeth Hospital, Gateshead, UK) debated the advantages and disadvantages of treating subclinical hypothyroidism

Subclinical hypothyroidism is associated with increased occurrence of cardiovascular events. Some – but not all - clinicians believe that the condition should be treated, especially in certain patient groups (such as the elderly).

Treating subclinical hypothyroidism may prevent the onset of further cardiovascular complications, said Dr Razvi.

However, treatment may ‘medicalize’ normal conditions or neglect other causes of symptoms such as fatigue or weight gain, argued Dr Biondi.

If treatment of subclinical hypothyroidism is considered, absolute values of thyroid stimulating hormone (TSH) should be evaluated.

TSH Levels persistently > 10 mIU/L indicate an increased risk of heart failure and cardiovascular mortality; L-thyroxine treatment should be considered

For TSH levels persistently between 5 and 10 mIU/L, the individual’s risk of cardiovascular disease and age should be evaluated, before treatment is considered
Periodic follow-up should be undertaken in any patient receiving treatment for subclinical hypothyroidism, to ensure that treatment remains appropriate
Age-specific reference ranges for serum TSH should be used. Dr Razvi emphasized this is in line with international recommendations.

Diabetes in pregnancy

Workshops led by Professor Osama Hamdy (Joslin Diabetes Centre, Boston, USA) Harvard Medical School focused on the diagnosis and treatment of diabetes in pregnancy

Gestational diabetes mellitus (GDM) requires prompt and accurate diagnosis and treatment. Rates of serious perinatal complications are reduced, and maternal health-related quality of life is improved, when GDM is promptly identified and treated.

Presently there is no international consensus on the criteria for GDM screening and diagnosis. The American Diabetes Association (ADA) basic recommendations are outlined in Figure 5, but further research is needed to establish a uniform approach to diagnosing GDM, explained Professor Hamdy.

Prenatal: Screen for diabetes mellitus at first prenatal visit in those with risk factors, using standard diagnostic criteria

During Pregnancy: Screen for GDM at 24–28 weeks’ gestation in women not previously known to have diabetes
Postpartum: Screen women with GDM for persistent diabetes at 6–12 weeks’ postpartum, using oral glucose tolerance test (OGTT)
Women who develop GDM should have lifelong screening for diabetes/pre-diabetes at least every 3 years
Women with a history of GDM who develop pre-diabetes should receive lifestyle or drug interventions to prevent diabetes

Two procedures can be used to diagnose GDM:

The one-step approach (IADPSG): 75g OGTT at 24-28 weeks’ gestation in women not previously diagnosed with diabetes
The test is performed in the morning after an overnight fast; fasting plasma glucose is measured at 1 and 2 h and GDM is diagnosed if any of the following plasma glucose values are exceeded:

  • o Fasting: ≥92 mg/dL (5.1 mmol/L)
  • o 1 h: ≥180 mg/dL (10.0 mmol/L)
  • o 2h: ≥153 mg/dL (8.5 mmol/L)

 

The two-step approach (NIH consensus): 50g nonfasting glucose test at 24-28 weeks’ gestation in women not previously diagnosed with diabetes

  • o If the plasma glucose level at 1h is ≥140 mg/dL (7.8 mmol/L), fasting 100g OGTT is performed
  • o GDM is diagnosed if the plasma glucose level at 3h is ≥140 mg/dL (7.8 mmol/L)

 

Managing GDM

GDM treatment begins immediately on diagnosis, with diet and exercise regimens.

Specialist referral is necessary because drug treatment with metformin, selected sulphonylureas or insulin may be required, as pregnancy progresses. 

Strict glycaemic targets are sometimes recommended for GDM: ≤ 5.0 mmol/L preprandial;  ≤ 120 mg/dL postprandial, with glycosylated haemoglobin < 5.0%.
Self-monitoring of blood glucose (SMBG) should be undertaken ≥3 times daily, and before any exercise or critical task (e.g. driving) is undertaken.

Combining measurement of glycosylated haemoglobin with frequent SMBG, or continuous glucose monitoring, helps women to achieve target glucose levels safely, added Professor Hamdy: SMBG alone can miss certain high glucose values.

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Target audience
diabetologists, Endocrinologists, Healthcare professionals
EACCME®
by Excemed
Endocrinology and metabolism