The change in glycaemic control immediately after COVID-19 vaccination in people with type 1 diabetes.

AIMS: Evidence suggests that some people with type 1 diabetes mellitus (T1DM) experience temporary instability of blood glucose (BG) levels after COVID-19 vaccination. We aimed to assess this objectively. METHODS: We examined the interstitial glucose profile of 97 consecutive adults (age ≥ 18 years) with T1DM using the FreeStyle Libre® flash glucose monitor in the periods immediately before and after their first COVID-19 vaccination. The primary outcome measure was percentage (%) interstitial glucose readings within the target range 3.9-10 mmol/L for 7 days prior to the vaccination and the 7 days after the vaccination. Data are mean ± standard error. RESULTS: There was a significant decrease in the % interstitial glucose on target (3.9-10.0) for the 7 days following vaccination (mean 52.2% ± 2.0%) versus pre-COVID-19 vaccination (mean 55.0% ± 2.0%) (p = 0.030). 58% of individuals with T1DM showed a reduction in the 'time in target range' in the week after vaccination. 30% showed a decrease of time within the target range of over 10%, and 10% showed a decrease in time within target range of over 20%. The change in interstitial glucose proportion on target in the week following vaccination was most pronounced for people taking metformin/dapagliflozin + basal bolus insulin (change -7.6%) and for people with HbA1c below the median (change -5.7%). CONCLUSION: In T1DM, we have shown that initial COVID-19 vaccination can cause temporary perturbation of interstitial glucose, with this effect more pronounced in people talking oral hypoglycaemic medication plus insulin, and when HbA1c is lower.

Analysis of continuous glucose tracking data in people with type 1 diabetes after COVID-19 vaccination reveals unexpected link between immune and metabolic response, augmented by adjunctive oral medication.

INTRODUCTION: The COVID-19 vaccination programme is under way worldwide. Anecdotal evidence is increasing that some people with type 1 diabetes mellitus (T1DM) experience temporary instability of blood glucose (BG) levels post-vaccination which normally settles within 2-3 days. We report an analysis of BG profiles of 20 individuals before/after vaccination. METHODS: We examined the BG profile of 20 consecutive adults (18 years of age or more) with T1DM using the FreeStyle Libre flash glucose monitor in the period immediately before and after COVID-19 vaccination. The primary outcome measure was percentage (%) BG readings in the designated target range 3.9-10 mmmol/L as reported on the LibreView portal for 7 days prior to the vaccination (week -1) and the 7 days after the vaccination (week +1). RESULTS: There was a significant decrease in the %BG on target following the COVID-vaccination for the 7 days following vaccination (mean 45.2% ± SE 4.2%) vs pre-COVID-19 vaccination (mean 52.6% ± SE 4.5%). This was mirrored by an increase in the proportion of readings in other BG categories 10.1%-13.9%/≥14%. There was no significant change in BG variability in the 7days post-COVID-19 vaccination. This change in BG proportion on target in the week following vaccination was most pronounced for people taking Metformin/Dapagliflozin+basal-bolus insulin (-23%) vs no oral hypoglycaemic agents (-4%), and median age <53 vs ≥53 years (greater reduction in %BG in target for older individuals (-18% vs -9%)). CONCLUSION: In T1DM, we have shown that COVID-19 vaccination can cause temporary perturbation of BG, with this effect more pronounced in patients talking oral hypoglycaemic medication plus insulin, and in older individuals. This may also have consequences for patients with T2DM who are currently not supported by flash glucose monitoring.

Dapagliflozin: an effective adjunctive treatment in type 1 diabetes.

INTRODUCTION: Many people with type 1 diabetes (T1DM) continue to run high HbA1c levels with an associated elevated risk of cardiovascular events and increased mortality. We describe here how adjunctive prescription of an SGLT2 inhibitor has improved the glycaemic control of several people with T1DM, where the new technology has been intensively deployed. METHODS: We report outcomes of six adults with T1DM who have been given dapagliflozin in East Cheshire, UK. Initiation was with education/support from the diabetes specialist nurses. All had an HbA1c of 70 mmol/mol (8.6%) or more before this was initiated. All had been monitoring glycemia with a FreeStyle Libre monitor for at least 6 months prior to this. RESULTS: The age range was 30-68 years. The mean duration of T1DM was 23.3 ± 5.5 years. All were on a basal-bolus regime. Over a 6 month period, HbA1c fell from 78.5 mmol/mol (9.3%) to 55 mmol/mol (7.2%). The greatest reduction in HbA1c was 57 mmol/mol (7.4%). Analysis of the FreeStyle Libre blood glucose records showed that the proportion of blood glucose readings on target (4-10 mmol/L) increased from 33.1 to 65.2% with the addition of dapagliflozin(P = 0.007). The proportion of blood glucose readings above target (>10 mmol/L) decreased from 68.0 to 26.4%, 6 months after initiation of dapagliflozin (P = 0.005). There was no increase in symptomatic hypoglycemia. CONCLUSION: Dapagliflozin as adjunctive therapy to basal-bolus regime insulin in individuals with T1DM was well tolerated and improved glycemic control with no increase in hypoglycemia. We provide further evidence of the value of this intervention.

The FreeStyle Libre flash glucose monitoring system: how it has improved glycaemic control for people with type 1 diabetes in Eastern Cheshire, UK.

INTRODUCTION: Many people with type 1 diabetes continue to run high HbA1c levels with associated elevated risk of cardiovascular events and increased mortality. We describe here how use of the FreeStyle Libre flash monitor has improved the glycaemic control of many people with type 1 diabetes where the new technology has been intensively deployed. METHODS: We report the outcomes of 92 consecutive adults (18 years of age or more) with type 1 diabetes who have begun using the FreeStyle Libre flash glucose monitor in East Cheshire, UK. Initiation was with education and support from one of the diabetes specialist nurses. An HbA1c of 60 mmol/mol (7.6%) was taken as the threshold for suboptimal glycaemic control. RESULTS: The mean cohort age was 43 years for men and 39 years for women (overall range 17-83 years). In 92 consecutive users, HbA1c decreased by an average of 10.7 mmol/mol (0.98%) after 3 months, and by 16.1 mmol/mol (1.47%) after 6 months. There was also a narrowing of the distribution of HbA1c, with many fewer people running high HbA1c ≥80 mmol/mol (9.5%). After the 6-month follow-up, two 2/92 users did not wish to continue with the monitoring. CONCLUSION: Flash glucose monitoring has great potential for the management of type 1 diabetes in the adult population and improving metabolic control/quality of life for people across the world. The technology provides significantly more data than the intermittent results obtained by traditional subcutaneous blood glucose monitoring, which may not capture intervals of extreme variability or nocturnal events.

Nocturia in interstitial cystitis/painful bladder syndrome.

OBJECTIVES: To explore the roles of pain and urgency in the nocturia of patients with interstitial cystitis/painful bladder syndrome (IC/PBS). METHODS: In a longitudinal study of incident IC/PBS cases, we assessed the associations of the presence and severity of nocturia with the presence and severity of pain and urgency, using multivariate analyses when necessary. Additionally, we simply asked patients with IC/PBS what awakens them at night. RESULTS: The multivariate analyses revealed associations of urgency with the presence and severity of nocturia and of bladder pain with the severity of nocturia. Direct queries of patients with IC/PBS about urgency and the reasons for awakening demonstrated that bladder pain might have played a twofold role: directly in awakening a large minority of patients and possibly indirectly in the majority by generating the sensation of urgency. CONCLUSIONS: These findings are consistent with urinary urgency and bladder pain each being in the causal pathway leading to nocturia in patients with IC/PBS.

Interstitial cystitis/painful bladder syndrome: what do patients mean by "perceived" bladder pain?

OBJECTIVES: To report the reasons patients with interstitial cystitis/painful bladder syndrome (IC/PBS) give for the perception that the bladder is the source of their pain. The perception that the bladder is the source of pain is a necessary criterion for many definitions of IC/PBS. METHODS: Events Preceding Interstitial Cystitis was a case-control study seeking risk factors for IC/PBS. The inclusion criteria for incident cases included "lower abdominal pain" or "bladder pain" and ≥2 of the following symptoms: urinary frequency, urgency, and/or nocturia. The patients were systematically followed and at 18 months after the baseline interview were asked an open-ended question about their reasons for perceiving the bladder to be the source of their pain. RESULTS: Of the 179 patients with current pain, 164 (92%) claimed ≥1 bladder or lower urinary tract symptoms caused them to perceive that their pain involved the bladder. Of these, 41% noted a "bladder" location for their pain; 34% noted pain increasing with bladder filling and/or decreasing with bladder emptying; 31% claimed the presence of urgency and/or frequency; 23% described worsened pain during and/or after urination; and 17% mentioned other urinary symptoms. Finally, 8% noted only nonurinary symptoms (4 patients) or "do not know" (11 patients). CONCLUSIONS: No predominant reason was found that patients with IC/PBS gave for suspecting the bladder to be the source of pain. The common reasons included pain location, changes with the urinary cycle, and an association with other urinary symptoms. To clarify the relationship of IC/PBS to other chronic pain syndromes, which often are comorbidities, these features of IC/PBS should be queried.

A prospective early history of incident interstitial cystitis/painful bladder syndrome.

PURPOSE: The longitudinal history of interstitial cystitis/painful bladder syndrome has been studied infrequently. In a national sample of incident cases we assessed changes in symptoms during the first several years of interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: We recruited 312 women with a history of interstitial cystitis/painful bladder syndrome symptoms of 12 months or less and interviewed them by telephone at baseline, and 6, 12, 18, 24, 36 and 48 months later. We queried symptoms in the last week and interval medication use. Individual and composite symptom categories were constructed. RESULTS: The median history of symptoms at study enrollment was 9 months. Median followup was 33 months after onset. The 57 study withdrawals (18%) were not substantively different than those remaining in followup. Many cases of severe and moderate interstitial cystitis/painful bladder syndrome at enrollment improved with time. As followup progressed, increasing proportions reported improvement while decreasing proportions reported symptom worsening. Of the women 27 (9%) reported at least temporary symptom remission. CONCLUSIONS: Of 304 women with incident interstitial cystitis/painful bladder syndrome 35% reported improvement from baseline in symptoms at last followup a median of 33 months after onset. However, the disappearance of all symptoms at any followup was uncommon.

Urinary tract infection and inflammation at onset of interstitial cystitis/painful bladder syndrome.

OBJECTIVES: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic disease primarily in women that is of low incidence and unknown etiology and manifests as bladder pain and urinary symptoms. Acute urinary tract infection (UTI) is of high incidence in women, presents as dysuria and urinary symptoms, and is caused by uropathogenic bacteria. We hypothesized that UTI is present at the onset of IC/PBS in some women. METHODS: For a case-control study seeking risk factors for IC/PBS, women with IC/PBS symptoms of 12 months or less were recruited and evaluated by interview and medical record review. The date of symptom onset was identified by a six-step process. Three evidence-based methods using culture, urinalysis, and symptoms were used separately and in combination to diagnose UTI at IC/PBS onset. RESULTS: Of 1177 screened women, 314 with recent-onset IC/PBS, including numerous confirming characteristics, were enrolled in the study; 98% of the requested medical records were obtained and reviewed. Evidence of a UTI at the onset of IC/PBS was found in 18% to 36% of women. Common UTI features not used in its diagnosis (short interval to medical care, hematuria, antibiotic treatment, and improvement after antibiotics) were significantly more common in those with onset UTI than in those without. CONCLUSIONS: These retrospective data suggest that a proportion, probably a minority, of women at IC/PBS onset had evidence of UTI or inflammation. Our results indicate that UTI is present at the onset of IC/PBS in some women and might reveal clues to IC/PBS pathogenesis.

Assessing urgency in interstitial cystitis/painful bladder syndrome.

OBJECTIVES: Interstitial cystitis/painful bladder syndrome (IC/PBS) at present is a symptom-based diagnosis. The Interstitial Cystitis Symptom Index (ICSI), also known as the O'Leary-Sant Symptom Index, is a widely used scale that assesses the four cardinal symptoms of IC/PBS (ie, bladder pain, urgency, frequency, and nocturia), by asking how often each is experienced. In an ongoing case-control study of recent-onset IC/PBS, we compared the ICSI with a series of questions that addressed the severity of these symptoms. METHODS: Recruiting nationally, we enrolled women with IC/PBS symptoms of 12 months' duration or less. We assessed the severity of pain, frequency, and urgency using Likert and categorical scales, and how often these symptoms were experienced using the ICSI. We compared these scales by frequency distributions and interscale correlations. RESULTS: In 138 women with recent-onset IC/PBS, the scores for frequency were correlated and, for pain, appeared to be complementary. However, for urgency, the ICSI question of "the strong need to urinate with little or no warning" consistently yielded lower scores than the severity question of "the compelling urge to urinate that is difficult to postpone." Some patients denied urgency to the ICSI question yet reported intense urgency to the severity question. CONCLUSIONS: Compared with the severity question, the ICSI underestimated the prevalence and degree of urgency. This observation is consistent with the views of others that sudden urgency does not define the sensation experienced by many patients with IC/PBS. Clarifying this symptom description may assist in developing a usable case definition for IC/PBS.

Using the International Continence Society's definition of painful bladder syndrome.

OBJECTIVES: To determine what proportion of patients with recent-onset interstitial cystitis (IC)/painful bladder syndrome (PBS) met the International Continence Society (ICS) definition and how those who met the definition differed from those who did not. METHODS: We recruited women who had recent-onset IC/PBS for an ongoing case-control study to identify its risk factors and studied our first 138 eligible patients to identify those who met the ICS definition. We then compared those who met the definition with those who did not by variables acquired from interviews and medical records. RESULTS: The 138 participants had intensities of pain, urgency, frequency, and nocturia, as well as O'Leary-Sant Symptom Index scores, similar to those of previously reported patients with IC/PBS. Six percent of cystoscopies demonstrated Hunner's ulcers, and 89% of hydrodistensions under anesthesia revealed glomerulations. The most liberal interpretation of the ICS definition did not include 47 (34%) of our patients. Comparing these with the 91 (66%) who did meet the ICS criteria, we found that 96 of 97 clinical variables, including many generally thought to be characteristic of IC/PBS, were not significantly different between the two groups. CONCLUSIONS: The ICS definition identified only 91 (66%) of the 138 patients whom study investigators and caregivers diagnosed as having IC/PBS. Furthermore, those who met the ICS definition did not differ in important ways from those who did not. These observations taken together suggest that the ICS definition may not be sufficiently sensitive. Minor modifications of the definition appeared to increase its sensitivity. Validation of a case definition (ie, assessing its sensitivity and specificity) would require testing it in patients with IC/PBS, as well as in patients with other diseases with similar symptoms.